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Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors
This phase I trial studies the safety of transplantation with a haploidentical donor
peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with
the immunomodulating drug, Zoledronate, given in the post-transplant period to treat
pediatric patients with relapsed or refractory hematologic malignancies or high risk solid
tumors.
Christian Capitini, MD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
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Inclusion Criteria:
• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable
unrelated donor OR time needed to find an acceptable unrelated donor match would
likely result in disease progression such that the patient may become ineligible for
any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is
deemed indicated (relapse occurring < 30 months from diagnosis, patients
relapsing after previous allogeneic transplant, relapse after 2nd remission,
primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial
Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem
cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd
remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome
Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive
auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor
or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with
conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery
and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance
score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central
Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective
birth control method
• Informed consent from patient or legal guardian (if patient is minor)
Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based
products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to
relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation;
and
• The results of donor testing for relevant communicable disease agents in
accordance with 1271.80 and 1271.85 are negative or nonreactive, except as
provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient
HLA class I ligands defined as the donor expressing a KIR gene for which the
corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi •EIA (Chagas)
Exclusion Criteria:
• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not
covered by other exclusion criteria expected to significantly increase the risk of
HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which
could interfere with the ability of the subject (or the only parent or legal guardian
available to care for the subject) to understand or adhere to the requirements of the
study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges
such enrollment would not interfere with endpoints of this study)
Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Ill-Defined Sites, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma
Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab
followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by
nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread
to other parts of the body. The addition of cabozantinib to the usual treatment may make it
work better. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may
help the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of
the enzymes needed for cell growth. It is not yet known how well the combination of
cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in
treating patients with renal cell cancer that has spread to other parts of the body.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03793166
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Inclusion Criteria:
• STEP I REGISTRATION CRITERIA
• Histologically documented renal cell carcinoma with clear cell component, including
patients who have sarcomatoid or rhabdoid features
• Any metastatic disease, including visceral, lymph node, other soft tissue and bone,
measurable per RECIST 1.1.
• Measurable disease as defined in the protocol.
• Must be intermediate or poor risk patient per International Metastatic Renal Cell
Carcinoma Database (IMDC) criteria (1 or more of the following): Karnofsky performance
status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic
treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN],
corrected calcium concentration greater than upper limit of normal [ULN], absolute
neutrophil count greater than ULN, platelet count > ULN).
• Central nervous system (CNS) disease permitted, if stable and not otherwise causing
symptoms or needing active treatment.
• Karnofsky performance status >= 70%.
• No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not
limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab,
tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting
T-cell co-stimulation or checkpoint pathways. The only exception is for prior
treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or
post-operative trials, as long as > 1 year since completion of systemic therapy.
• No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [> 28 days]
and prior adjuvant sunitinib > 180 days since completion and prior immunotherapy as
above are allowed).
• No systemic cancer therapy less than 28 days prior to registration; no radiation
therapy less than 14 days prior to registration. There must be a complete recovery and
no ongoing complications from radiotherapy.
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative serum or urine pregnancy test done =< 14 days prior to
registration is required.
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Hemoglobin >= 8 g/dL.
• Calculated (Calc.) creatinine clearance >= 30 mL/min.
• Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known
or likely Gilbert's syndrome, for whom total bilirubin up to 3 mg/dL is allowed with
direct bilirubin =< 20% total bilirubin)
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of
normal (ULN) or < 5 x ULN if hepatic metastases present.
• STEP 2 REGISTRATION ELIGIBILITY CRITERIA
• Successful completion of at least 1 cycle of ipilimumab/nivolumab.
• Resolution of any treatment-related adverse events to grade 1 or less per dose
modification section (this criteria does not include any adverse events [AEs] not
attributable to treatment which are present due to disease), with
prednisone-equivalent dosing at 10 mg daily or less. Exceptions for this criteria
include patients receiving replacement hormone treatments (such as levothyroxine for
treatment-related hypothyroidism or glucocorticoid replacement for adrenal
insufficiency). Please contact study chair if further discussion is needed.
• No more than 80 days from last dose of ipilimumab/nivolumab.
Exclusion Criteria:
• Active autoimmune disease requiring ongoing therapy.
• Ongoing acute toxicity > grade 2 from previous treatment.
• History of severe allergic, anaphylactic or other hypersensitivity reactions to
chimeric or humanized antibodies.
• Active hepatitis B/C, or active tuberculosis (PPD response without active TB is
allowed)
• Human immunodeficiency virus (HIV) -infected patients with detectable viral load
within 6 months prior to registration. Patients on effective anti-retroviral therapy
with undetectable viral load within 6 months prior to registration are eligible.
• Concurrent use of immunosuppressive medication including prednisone above 10 mg daily.
• Uncontrolled adrenal insufficiency.
• Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP > 90
mmHg).
• Major surgery less than 28 days prior to registration.
• Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to
registration.
• Any arterial thrombotic events within 180 days prior to registration.
• Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to
registration.
• Cavitating pulmonary lesions or known endotracheal or endobronchial disease
manifestations.
• Lesions encasing or invading any major blood vessels (this does not include tumor
thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with
tumor thrombus extending into/through renal vein are considered eligible.
• Moderate of severe hepatic impairment (Child-Pugh B or C).
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180
days prior to registration. (Any asymptomatic, treated pulmonary embolism or
asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed).
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms.
• Unstable cardiac arrhythmia within 6 months prior to registration.
• Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of
pulmonary hemorrhage =< 90 days prior to registration.
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess,
bowel obstruction, or gastric outlet obstruction within 180 days prior to
registration.
• Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome
within 28 days prior to registration.
• Untreated hypothyroidism (treated hypothyroidism on thyroid replacement therapy is
allowed. Abnormal thyroid-stimulating hormone (TSH) is acceptable with normal T3/free
T4 if treated on thyroid replacement therapy)
• Evidence of pancreatitis, history of organ transplant, or history of congenital QT
syndrome.
• Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors
(e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g.,
clopidogrel) within 5 days of registration. Allowed anticoagulants include:
prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of
LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban,
apixaban. Allowed also in patients with known brain metastases who are on a stable
dose of the anticoagulant for at least 1 week prior to registration without clinically
significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or
non-ST elevation myocardial infarction [NSTEMI]) within 6 months or active NY Heart
Association class 3-4 heart failure symptoms
Clear Cell Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Lymph Nodes, Metastatic Malignant Neoplasm in the Soft Tissues, Metastatic Malignant Neoplasm in the Viscera, Sarcomatoid Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Kidney
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)
The primary Phase 1 purpose of this study was to assess overall safety, tolerability and
recommended Phase 2 dose (RP2D) of APL-101.
The Phase 2 portion will assess efficacy of the dose determined in Phase 1 in individuals
with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations; individuals with cancers
associated with c-Met amplifications; individuals with cancers associated with c-Met fusion
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03175224
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Major
Inclusion Criteria:
• Able to understand and comply with study procedures, understand the risks involved,
and provide written informed consent.
• For Phase 1, histologically and / or cytological confirmed unresectable or metastatic
solid malignancy, refractory to standard therapies with no more than three prior lines
of therapy (Completed).
• For Phase 2, seven cohorts will be enrolled:
Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2:
NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of
prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic
progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high
level amplification (except Primary CNS tumors), Cohort C-1: NSCLC harboring MET
amplification and wild-type epidermal growth factor receptor (EGFR) with no more than 3
lines of prior therapy (MET Naive), Cohort D: basket of tumor types except for primary CNS
tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary
cancer). Previously treated; or previously untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic
setting). Met naive, Cohort E: Primary CNS tumors with MET alterations (single or
co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or
MET amplification).Previously treated or previously untreated but refused standard
treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), Met naive.
•Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is
required (except in Cohort A-1 in the US and Cohort C-1).
In Phase 2, provision of either archival or a fresh tumor biopsy sample (if safe and
feasible) either from the primary or a metastatic site is required for study entry for
Cohorts A-1, A-2, C, C-1, and D.
• Measurable disease according to relevant criteria (RECIST v1.1, RANO for CNS tumors,
or other relevant criteria per tumor type).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and/or Karnofsky
Performance Scale (KPS) score.
• For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted
agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the
agents used, whichever is shorter, must have elapsed, and any encountered toxicity
must have resolved to levels meeting all the other eligibility criteria prior to the
first dose of study treatment. Palliative radiotherapy to non-target lesions should be
completed within 2 weeks prior to APL-101 administration.
• No planned major surgery within 4 weeks of first dose of APL-101
• Expected survival (life expectancy) ≥ 3 months from C1D1.
Major
Exclusion Criteria:
• Hypersensitivity to APL-101, excipients of the drug product, or other components of
the study treatment regimen.
• Known actionable mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1,
RET, NTRK, KRAS, and BRAF.
• Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101,
symptomatic or unstable arrhythmia requiring medical therapy, history of congenital
prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at
screening (> 450 msec based on the average of 3 measurements), or concurrent treatment
with a medication that is a known risk for prolonging the QT interval.
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active
inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption
syndrome).
Symptomatic and/or neurologically unstable CNS metastases, or who require an increase in
steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose
for at least 2 weeks prior to C1D1 may be allowed.
•Women who are breastfeeding.
Solid Tumor, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Assessing the Clinical Benefit of Molecular Profiling in Patients With Solid Tumors
Many patients are treated for advanced cancer without knowledge of underlying molecular
features that might indicate FDA approved therapies or potential eligibility for
biomarker-selected clinical trials.
The Strata Trial (STR-001-001) has been initiated by Strata Oncology to evaluate the clinical
benefit of systematic comprehensive genomic profiling for participants with advanced cancer
using real-world data and endpoints, while assessing the proportion of participants available
for clinical trials and approved targeted therapies in advanced and/or aggressive cancers.
The Strata Trial uses surplus, or leftover, tumor specimens for molecular profiling and does
not require additional study-specific procedures.
Mark Burkard, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03061305
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Inclusion Criteria:
• Subjects must be ≥ 18 years of age.
• Subjects must have histologically documented solid tumors (including lymphoma and
multiple myeloma).
• Specific criteria for individual tumor types are as follows:
1. Participants with gliomas are eligible at any stage of disease
2. Participants with pancreatic carcinoma are eligible at any stage of disease
3. Participants with rare tumors (i.e. cancer started in an unusual place in the
body, it is unusual type and requires special treatment) are eligible at stages
II-IV.
4. Participants with other tumor types must have recurrent, relapsed, refractory,
metastatic, or advanced stages III or IV cancer.
• Must have an adequate formalin-fixed paraffin-embedded tumor specimen for genomic
sequencing.
Cancer, Adult Solid Tumor, Lymphoma, Multiple Myeloma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Melanoma/Skin cancer, Sarcoma, Uterus
Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma
This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab
work with or without eflornithine in treating patients with neuroblastoma that has come back
(relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy,
such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth
of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping
them from spreading. Immunotherapy with monoclonal antibodies, such as dinutuximab, may
induce changes in the body's immune system and may interfere with the ability of tumor cells
to grow and spread. Eflornithine blocks the production of chemicals called polyamines that
are important in the growth of cancer cells. Giving eflornithine with irinotecan
hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with
relapsed or refractory neuroblastoma.
Kenneth Desantes, M.D.
All
1 Year and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03794349
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Inclusion Criteria:
• Patients must have had histologic verification of neuroblastoma or
ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with
elevated urinary catecholamines (i.e. > 2 x upper limit of normal [ULN]), at the time
of initial diagnosis.
• For the purposes of this study, aggressive multidrug chemotherapy is defined as
chemotherapy including 2 or more agents that must include an alkylating agent and a
platinum-containing compound as intended to treat high-risk disease. The doses of
chemotherapy must be comparable to those used in frontline high-risk neuroblastoma
therapies (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, and ANBL1531).
Patients must have ONE of the following:
• First episode of recurrent high-risk disease following completion of aggressive
multi-drug frontline high-risk therapy.
• First episode of progressive high-risk disease during aggressive multi-drug
frontline therapy.
• Primary resistant/refractory disease (less than partial response by International
Neuroblastoma Response Criteria [INRC]) detected at the conclusion of at least 4
cycles of aggressive multidrug induction chemotherapy on or according to a
high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1,
ANBL12P1, ANBL1531, etc.).
• Patients must have at least ONE of the following at the time of enrollment:
• Measurable tumor on magnetic resonance imaging (MRI) or computed tomography (CT)
scan. Measurable is defined as >= 10 mm in at least one dimension on
spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates
increased fludeoxyglucose F-18 (FDG) uptake on positron emission tomography (PET)
scan.
• MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one
site. This site must represent disease recurrence after completion of therapy,
progressive disease on therapy, or refractory disease during induction.
• Patients with resistant/refractory soft tissue disease that is not MIBG avid or
does not demonstrate increased FDG uptake on PET scan must undergo biopsy to
document the presence of viable neuroblastoma. Biopsy is not required for
patients who have a new site of soft tissue disease (radiographic evidence of
disease progression) regardless of whether progression occurs while receiving
therapy or after completion of therapy.
• Patients with bone marrow disease only will be eligible if they have more than 5%
disease involvement (documented neuroblastoma cells) in at least one sample from
bilateral bone marrow biopsies.
• Note: Patients with elevated catecholamines (i.e. > 2 x ULN) only are NOT
eligible for this study.
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age.
• Primary refractory/resistant patients must have received at least 4 cycles of
frontline high-risk chemotherapy. Frontline therapy may also have included surgery,
chemotherapy, autologous stem cell transplantation (SCT) +/- MIBG, immunotherapy,
radiotherapy, and retinoids but must NOT have received second line therapy for
resistant/refractory, relapsed, or progressive disease. Patients who received
intensified therapy for poor induction response or refractory disease (e.g. MIBG) will
be considered to have received second line therapy and will not be eligible.
• At least 14 days must have elapsed since completion of myelosuppressive therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced
platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of
agent.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and
toxicity related to prior antibody therapy must be recovered to grade =< 1.
• No interim time prior to study entry is required following prior radiation therapy
(RT) for non-target lesions. However, patients must not have received radiation for a
minimum of 4 weeks prior to study entry at the site of any lesion that will be
identified as a target lesion to measure tumor response. Lesions that have been
previously radiated cannot be used as target lesions unless there is radiographic
evidence of progression at the site following radiation or a biopsy done following
radiation shows viable neuroblastoma. Palliative radiation while on study is not
permitted.
• Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell
infusions (including stem cell infusions given as supportive care following 131 I-MIBG
therapy) as long as hematologic and other eligibility criteria have been met.
• Patients are eligible >= 6 weeks after therapeutic 131 I-MIBG provided that all other
eligibility criteria are met.
• Subjects who have previously received anti-GD2 monoclonal antibodies with or without
retinoids for biologic therapy are eligible unless they have had progressive disease
while receiving prior anti-GD2 therapy or progressed/relapsed within 3 months of
receiving anti-GD2 therapy. However, eligible patients may NOT have received anti-GD2
monoclonal antibodies in combination with chemotherapy.
• Subjects who have received autologous marrow infusions or autologous stem cell
infusions that were purged using monoclonal antibody linked to beads are eligible.
• Subjects who have previously received DFMO are eligible for this study provided they
have not had progressive disease while receiving DFMO or progressed/relapsed within 3
months of completing DFMO.
• Patients must not have received long-acting myeloid growth factors (e.g.
pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed
since administration of a short-acting myeloid growth factor.
• For patients with solid tumors (without marrow involvement) including status post SCT:
peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to
enrollment).
• For patients with solid tumors (without marrow involvement) including status post SCT:
platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Patients known to have bone marrow involvement with neuroblastoma are eligible
provided that minimum ANC and transfusion independent platelet count criteria are met
(as above). However, these patients are not evaluable for hematological toxicity.
• Creatinine clearance or radioisotope GFR >= 70 mL/min/1.73 m^2 or a serum creatinine
based on age/gender as follows:
• 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
• 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
• 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
• 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
• 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
• >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to
enrollment).
• Total bilirubin =< 1.5 x ULN for age (within 7 days prior to enrollment).
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x
ULN for age (=< 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L
(within 7 days prior to enrollment).
• Shortening fraction of >= 27% by echocardiography (ECHO) (within 7 days prior to
enrollment).
• Ejection fraction of >= 50% by ECHO or gated radionuclide study (within 7 days prior
to enrollment).
• No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen
requirement, and room air pulse oximetry > 94% if there is a clinical indication for
pulse oximetry. Normal pulmonary function tests in patients who are capable of
cooperating with testing (including diffusion capacity of the lung for carbon monoxide
[DLCO)] are required if there is a clinical indication for determination. For patients
who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT
required.
• Patients with a history of central nervous system (CNS) disease must have no clinical
or radiological evidence of active CNS disease at the time of study enrollment.
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anti-convulsants.
• CNS toxicity =< grade 2.
Exclusion Criteria:
• Men and women of childbearing potential and their partners must agree to use adequate
contraception while enrolled on this study. Based on the established teratogenic
potential of alkylating agents, pregnant women will be excluded from this study.
Because of potential risks to breastfed infants due to drug metabolites that could be
excreted in breast milk, female patients who are lactating must agree to stop
breastfeeding or will otherwise be excluded from this study. Females of childbearing
potential must have a negative pregnancy test to be eligible for this study.
• Patients with only elevated catecholamines (i.e. > 2 x ULN) are NOT eligible for this
study.
• Patients must have been off pharmacologic doses of systemic steroids for at least 7
days prior to enrollment. Patients who require or are likely to require pharmacologic
doses of systemic corticosteroids while receiving treatment on this study are
ineligible. The only exception is for patients known to require 2 mg/kg or less of
hydrocortisone (or an equivalent dose of an alternative corticosteroid) as
premedication for blood product administration in order to avoid allergic transfusion
reactions. The use of conventional doses of inhaled steroids for the treatment of
asthma is permitted, as is the use of physiologic doses of steroids for patients with
known adrenal insufficiency.
Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not
eligible.
• Patients must not have received prior treatment with irinotecan and temozolomide.
• Patients must not have received enzyme-inducing anticonvulsants including phenytoin,
phenobarbital, or carbamazepine for at least 7 days prior to study enrollment.
Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic
acid, or levetiracetam will be eligible.
• Patients who have received drugs that are strong inducers or inhibitors of CYP3A4
within 7 days prior to study enrollment are not eligible.
• Patients must not have been diagnosed with myelodysplastic syndrome or with any
malignancy other than neuroblastoma.
• Patients with symptoms of congestive heart failure are not eligible.
• Patients must not have >= grade 2 diarrhea.
• Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not
be eligible for this trial. Additionally, patients with significant malabsorption will
not be eligible for this trial.
• Patients must not have uncontrolled infection.
• Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or
reactions that required permanent discontinuation of the anti-GD2 therapy are not
eligible.
• Patients with a significant intercurrent illness (any ongoing serious medical problem
unrelated to cancer or its treatment) that is not covered by the detailed exclusion
criteria and that is expected to interfere with the action of study agents or to
significantly increase the severity of the toxicities experienced from study treatment
are not eligible.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus, High Risk Neuroblastoma, Recurrent Neuroblastoma, Refractory Neuroblastoma
Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well larotrectinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with NTRK fusions that may
have spread from where it first started to nearby tissue, lymph nodes, or distant parts of
the body (advanced) and have come back (relapased) or does not respond to treatment
(refractory). Larotrectinib may stop the growth of cancer cells by blocking some of the
enzymes needed for cell growth.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03213704
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• APEC1621SC: Patient must have enrolled onto APEC1621SC and must have been given a
treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621A
based on the presence of an actionable mutation as defined in APEC1621SC
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment; patients with neuroblastoma who do not have measurable disease but have
MIBG+ evaluable disease are eligible; measurable disease in patients with CNS
involvement is defined as any lesion that is at minimum 10 mm in one dimension on
standard MRI or CT; Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post
radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age; Note: neurologic deficits in patients with CNS tumors must have been
relatively stable for at least 7 days prior to study enrollment; patients who are
unable to walk because of paralysis, but who are up in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required time frame,
the numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive;
for agents not listed, the duration of this interval must be discussed with the
study chair and the study-assigned research coordinator prior to enrollment
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy
(42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last
dose of agent; for agents not listed, the duration of this interval must be
discussed with the study chair and the study-assigned research coordinator prior
to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor leukocyte infusion (DLI) or boost infusion: >=
84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, NK cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial brain metastases (BM)
radiation; Note: radiation may not be delivered to "measurable disease" tumor
site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to other NTRK inhibitors including
but not limited to LOXO-101 (larotrectinib), entrectinib (RXDX-101), DS6051,
PLX7486
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to
enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment) (within 7 days
prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions); these patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL); male: 0.6 female: 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL); male: 0.8 female: 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL); male: 1 female: 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL); male: 1.2 female: 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL); male: 1.5 female: 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL); male: 1.7 female: 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment); (for the purpose of this study, the ULN for
SGPT is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients with seizure disorder may be enrolled if on anti-convulsants and well
controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE]
version [v] 5.0) resulting from prior therapy must be =< grade 2, with the exception
of decreased tendon reflect (DTR); any grade of DTR is eligible
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of
fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests
must be obtained in girls who are post-menarchal; males or females of reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study treatment
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of
corticosteroid for at least 7 days prior to enrollment are not eligible; if used to
modify immune adverse events related to prior therapy, >= 14 days must have elapsed
since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease (GVHD) post bone marrow transplant are not eligible for this
trial
• Patients who are currently receiving drugs that are strong inducers or inhibitors of
CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided
from 14 days prior to enrollment to the end of the study; Note: CYP3A4 inducing
anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose,
are allowed
• Patients who have received prior therapy with a specific inhibitor of TRK (including
but not limited to entrectinib [RXDX-101], DS-6051b, and PLX7486) are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic
alterations that have come back (recurrent) or does not respond to treatment (refractory) and
may have spread from where it first started to nearby tissue, lymph nodes, or distant parts
of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03213652
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the
presence of an actionable mutation
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment.
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on a standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively
stable for at least 7 days prior to study enrollment; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the
last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment
with other ALK inhibitors is permitted given that at least 5 half-lives or 21
days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to
enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment) (within 7 days
prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions); these patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on
age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for
female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for
female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for
female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL
for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL
for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for
female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT
is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study because there is
currently no available information regarding human fetal or teratogenic toxicities;
pregnancy tests must be obtained in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study treatment and for one week after the
last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
not eligible; if used to modify immune adverse events related to prior therapy,
>= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another
investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents
are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong
inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the
end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations
This phase II trial studies how well olaparib works in treating patients with glioma,
cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it
first started (primary site) to other places in the body (metastatic) and that does not
respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking
some of the enzymes needed for cell growth.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03212274
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Subjects must be able to understand the nature of this trial and provide written
informed consent, prior to any study specific procedures; patients with Impaired
Decision Making Capacity (IDMC) who have a close caregiver or legally authorized
representative (LAR) may be considered eligible for this study at the treating
physician's discretion, provided that the physician is reasonably sure that the
possible risks and benefits of the study are clear and that the patient will take the
drug as prescribed
• Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant
tumor that has progressed despite standard therapy, or for which no effective standard
therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated
with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2
mutation which must be detected in a clinical accredited laboratory using a Food and
Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid
(DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments
(CLIA)-certified laboratory; only specific mutations that lead to a neomorphic
phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S,
R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K
• Patients must have tumors determined to be easily accessible for biopsy and must be
willing to have serial biopsies (with a third biopsy upon evidence of disease
progression); in case of multiple lesions, tumor biopsies will be performed on the
most accessible site of disease; all possible precautions to avoid complications will
be taken, including discussions in multidisciplinary meetings, if needed; patients
affected by glioma will not be considered for study biopsies
• Patients must be willing to undergo extra blood sampling for correlative studies
• Subjects with extracranial disease must have evaluable disease by Response Evaluation
Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must
have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO)
criteria
• For subjects with glioma, specific inclusion criteria are as follows:
• The disease should be recurrent or transformed glioma; subjects must not have had
prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment
• There must be an enhancing component of disease, as evaluated on pre-treatment
magnetic resonance imaging (MRI)
• For patients with World Health Organization (WHO) grade III or IV glioma and
progressive disease < 12 weeks after completion of chemoradiotherapy, progression
can be defined by the following set of criteria:
• New enhancement outside of the radiation field (beyond the high-dose region
or 80% isodose line)
• If there is unequivocal evidence of viable tumor on histopathologic sampling
(e.g., solid tumor areas. i.e., > 70% tumor cell nuclei in areas), high or
progressive increase in MIB-1 proliferation index compared with prior
biopsy, or evidence for histologic progression or increased anaplasia in
tumor);
• Note: Given the difficulty of differentiating true progression from
pseudoprogression, clinical decline alone, in the absence of radiographic or
histologic confirmation of progression, will not be sufficient for
definition of progressive disease in the first 12 weeks after completion of
concurrent chemoradiotherapy
• For patients with WHO grade III or IV glioma and progressive disease >= 12 weeks
after completion of chemoradiotherapy, progression can be defined by the
following set of criteria:
• New contrast-enhancing lesion outside of radiation field on decreasing,
stable, or increasing doses of corticosteroids
• Increase by >= 25% in the sum of the products of perpendicular diameters
between the first post-radiotherapy scan, or a subsequent scan with smaller
tumor size, and the scan at 12 weeks or later on stable or increasing doses
of corticosteroids
• For patients receiving antiangiogenic therapy, significant increase in
T2/fluid attenuated inversion recovery (FLAIR) non-enhancing lesion may also
be considered progressive disease; the increased T2/FLAIR must have occurred
with the patient on stable or increasing doses of corticosteroids compared
with baseline scan or best response after initiation of therapy and not be a
result of comorbid events (e.g., effects of radiation therapy,
demyelination, ischemic injury, infection, seizures, postoperative changes,
or other treatment effects)
• Note: Clinical deterioration alone is not attributable to concurrent
medication or comorbid conditions is sufficient to declare progression on
current treatment but not for entry onto a clinical trial for recurrence
• For patients with WHO grade II glioma progression is defined by any one of the
following:
• Development of new lesions or increase of enhancement (radiological evidence
of malignant transformation)
• A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or
increasing doses of corticosteroids compared with baseline scan or best
response after initiation of therapy, not attributable to radiation effect
or to comorbid events
• For subject with extracranial disease, they must have at least one lesion, not
previously irradiated, that can be accurately measured at baseline as >= 10 mm in the
longest diameter (except lymph nodes which must have short axis >= 15 mm) with
computed tomography (CT) or magnetic resonance imaging (MRI) or >= 10 mm with calipers
by clinical exam OR at least one lesion (measurable and/or non-measurable) that can be
accurately assessed by CT/MRI/clinical exam at baseline and follow up visits
• Subjects must have progressive cancer at the time of study entry; prior experimental
(non-FDA approved) therapies (other than drugs that share the same target) and
immunotherapies are allowed; patients must not have received these therapies for 30
days or five half-lives of the drug (whichever is less) prior to the initiation of
study treatment; toxicities from these therapies should have recovered to =< grade 1,
with the exception of stable chronic grade 2 that is not overlapping with presumed
toxicities of olaparib
• Female/male of age >= 18 years. This is because no dosing or adverse event data are
currently available on the use of olaparib in patients < 18 years of age, children are
excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) 0-2 (Karnofsky >= 50%)
• Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days
prior to administration of study treatment)
• Leukocytes >= 3,000/mcL (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to
administration of study treatment)
• Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study
treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days
prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal unless liver metastases are present in
which case they must be =< 5 x ULN (within 28 days prior to administration of study
treatment)
• Creatinine clearance estimated using the actual body weight and Cockcroft-Gault
equation of >= 51 mL/min (within 28 days prior to administration of study treatment)
• Patients must have a life expectancy >= 16 weeks
• Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up
• No previous treatment with the specific assigned study drug or any other PARP
inhibitor
• Prior radiation therapy is allowed; patients must not have received radiation therapy
within 3 weeks prior to the initiation of study treatment
• Women of child-bearing potential are expected to use highly effective contraception
during the study and for 1 month after the last dose of study drug; postmenopausal or
evidence of non-childbearing status for women of childbearing potential: negative
urine or serum pregnancy test within 28 days of study treatment and confirmed prior to
treatment on day 1; postmenopausal is defined as one or more of the following:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the
post-menopausal range for women under 50
• Radiation-induced oophorectomy with last menses > 1 year ago
• Chemotherapy-induced menopause with > 1 year interval since last menses
• Surgical sterilization (bilateral oophorectomy or hysterectomy)
• Male patients and their partners, who are sexually active and of childbearing
potential, must agree to the use of two highly effective forms of contraception in
combination, throughout the period of taking study treatment and for 3 months after
last dose of study drug(s) to prevent pregnancy in a partner
Exclusion Criteria:
• Patients should not enter the study if any of the following exclusion criteria are
fulfilled
• Involvement in the planning and/or conduct of the study
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the
last 30 days or five half-lives of the drug (whichever is less) prior to the
initiation of study treatment (6 weeks for nitrosoureas or mitomycin C)
• Any previous treatment with PARP inhibitor, including olaparib
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin
cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ
(DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including
lymphomas (without bone marrow involvement) curatively treated with no evidence of
disease for >= 5 years; patients with a history of localized triple negative breast
cancer may be eligible, provided they completed their adjuvant chemotherapy more than
three years prior to registration, and that the patient remains free of recurrent or
metastatic disease
• Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec or family
history of long QT syndrome
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout
period prior to starting olaparib is 2 weeks; because the lists of these agents are
constantly changing, it is important to regularly consult a frequently updated drug
information reference; medical reference texts such as the Physicians' Desk Reference
may also provide this information; as part of the enrollment/informed consent
procedures, the patient will be counseled on the risk of interactions with other
agents, and what to do if new medications need to be prescribed or if the patient is
considering a new over-the-counter medicine or herbal product
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or
moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents; because the lists of these agents are constantly changing, it
is important to regularly consult a frequently updated drug information reference;
medical reference texts such as the Physicians' Desk Reference may also provide this
information; as part of the enrollment/informed consent procedures, the patient will
be counseled on the risk of interactions with other agents, and what to do if new
medications need to be prescribed or if the patient is considering a new
over-the-counter medicine or herbal product
• Persistent toxicities caused by previous cancer therapy; toxicities should have
recovered to =< grade 1, excluding alopecia and stable chronic grade 2 toxicity that
is not overlapping with presumed toxicities of olaparib
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of MDS/AML
• Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence
of brain metastases is not required; the patient can receive a stable dose of
corticosteroids before and during the study if these were started at least 4 weeks
prior to treatment; patients with spinal cord compression unless considered to have
received definitive treatment for this and evidence of clinically stable disease for
28 days; patients with known uncontrolled brain metastases should be excluded from
this clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events
• Major surgery within 2 weeks of starting study treatment; effects from surgeries
should have recovered to =< grade 1, with the exception of stable chronic grade 2 that
is not overlapping with presumed toxicities of olaparib
• Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection; examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder
that prohibits obtaining informed consent and would limit compliance with study
requirements
• Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication
• Women who are actively breast feeding
• Immunocompromised patients, e.g., patients who are known to be serologically positive
for human immunodeficiency virus (HIV); HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with Olaparib; in addition, these patients are at increased risk of
lethal infections when treated with marrow-suppressive therapy; appropriate studies
will be undertaken in patients receiving combination antiretroviral therapy when
indicated
• Patients with a known hypersensitivity to olaparib or any of the excipients of the
product; history of allergic reactions attributed to compounds of similar chemical or
biologic composition to olaparib
• Patients with known active hepatitis (i.e. hepatitis B or C) due to risk of
transmitting the infection through blood or other body fluids
• Previous allogeneic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT)
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red
blood cells and platelet transfusions are acceptable)
• Patients who are receiving any other investigational agents
• Pregnant women are excluded from this study because olaparib is an agent with the
potential for teratogenic or abortifacient effects; because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with olaparib, breastfeeding should be discontinued if the mother is treated
with olaparib
• Patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), or
features suggestive of MDS/AML
Advanced Malignant Solid Neoplasm, Glioblastoma, Recurrent Cholangiocarcinoma, Recurrent Glioma, Recurrent Malignant Solid Neoplasm, WHO Grade 2 Glioma, WHO Grade 3 Glioma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03155620
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and
=< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor
sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from
start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed
paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy
or surgery that was performed at any point after initial tumor recurrence/progression,
or be planned to have a procedure to obtain such a sample that is considered to be of
potential benefit by the treating clinicians; a tumor sample from a clinically
performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto
Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse
intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report
availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting
2022): In stage 2 of the study, no tumor samples will be submitted for centralized
clinical tumor profiling; instead, a tumor molecular profiling report from a College
of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments
(CLIA)-approved testing laboratory must be submitted for review by the Molecular
Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was
obtained at any point after initial tumor recurrence/progression and must be
accompanied by a pathology report for the same tumor specimen; a molecular
profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable
for enrollment onto Pediatric MATCH only for children with high-grade gliomas of
the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that
molecular profiling reports are available from multiple timepoints, the most
recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic
deficits in patients with central nervous system (CNS) tumors must have been stable
for at least 7 days prior to study enrollment; patients who are unable to walk because
of paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance
imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in
patients with CNS tumors must have been stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the performance
score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; if after the
required timeframe, the numerical eligibility criteria are met, e.g. blood count
criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be
myelosuppressive: for agents not listed, the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator prior to enrollment >= 21 days after the last dose of cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; for agents not listed, the duration of this interval
must be discussed with the study chair and the study-assigned research
coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of
antibody, and toxicity related to prior antibody therapy must be recovered
to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days
after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells,
etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not
be entered on this study due to risks of fetal and teratogenic adverse events as seen
in animal/human studies, or because there is currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Langerhans Cell Histiocytosis, Malignant Glioma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
This phase III trial studies iobenguane I-131 or lorlatinib and standard therapy in treating
younger patients with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma.
Radioactive drugs, such as iobenguane I-131, may carry radiation directly to tumor cells and
not harm normal cells. Lorlatinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth. Giving iobenguane I-131 or lorlatinib and standard therapy
may work better compared to lorlatinib and standard therapy alone in treating younger
patients with neuroblastoma or ganglioneuroblastoma.
Kenneth Desantes, M.D.
All
365 Days to 30 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03126916
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to
enrollment on ANBL1531 (NCT03126916)
• Patient must be >= 365 days and =< 30 years of age at diagnosis
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular)
verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone
marrow with elevated urinary catecholamine metabolites; the following disease groups
are eligible:
• Patients with International Neuroblastoma Risk Group (INRG) stage M disease are
eligible if found to have either of the following features:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to
reference signals), regardless of additional biologic features; OR
• Age > 547 days regardless of biologic features
• Patients with INRG stage MS disease with MYCN amplification
• Patients with INRG stage L2 disease with MYCN amplification
• Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS
disease who progressed to stage M without prior chemotherapy may enroll within 4
weeks of progression to stage M
• Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1
disease who progress to stage M without systemic therapy may enroll within 4
weeks of progression to stage M
• Patients initially recognized to have high-risk disease must have had no prior
systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis
and within allowed timing); patients observed or treated with a single cycle of
chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per
ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease
but subsequently found to meet the criteria will also be eligible; patients who
receive localized emergency radiation to sites of life-threatening or
function-threatening disease prior to or immediately after establishment of the
definitive diagnosis will be eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
• 1 to < 2 years: male = 0.6; female = 0.6
• 2 to < 6 years: male = 0.8; female = 0.8
• 6 to < 10 years: male = 1; female = 1
• 10 to < 13 years: male = 1.2; female = 1.2
• 13 to < 16 years: male = 1.5; female = 1.4
• >= 16 years: male = 1.7; female = 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x
ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by
echocardiogram or radionuclide angiogram
• No known contraindication to peripheral blood stem cell (PBSC) collection; examples of
contraindications might be a weight or size less than the collecting institution finds
feasible, or a physical condition that would limit the ability of the child to undergo
apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
• Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor
histology (may meet criteria for high risk classification but are not eligible for
this trial)
• Patients with bone marrow failure syndromes
• Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to
underlying medical disorders
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus, Ganglioneuroblastoma, Neuroblastoma
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects
with low risk germ cell tumors for recurrence after their tumor is removed. When the germ
cell tumors has spread outside of the organ in which it developed, it is considered
metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and
cisplatin, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. The trial studies
whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic
standard risk germ cell tumors.
Kenneth Desantes, M.D.
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT03067181
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Inclusion Criteria:
• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and
stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patient must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I
germ cell tumor; for the standard risk arms, patients must be newly diagnosed with
metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary
extracranial germ cell tumor in any of the categories outlined below is required of
all patients at enrollment except for those who were initially diagnosed with stage I
non-seminoma malignant GCT and later recur during observation post surgery off study;
for these patients, if elevated tumor markers rise to > 5 x upper limit of normal
(ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is
not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk
sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT);
tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage:
COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC)
testicular stage IA, IB and IS; histology: must contain at least one of the following:
yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular
stage IA IB, and IS; histology: must contain at least one of the following: may
contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus
Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) <
11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk;
histology: must contain at least one of the following: yolk sac tumor, embryonal
carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op:
alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) <
3.0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age
(years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the
study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components
of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with
other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac
tumor is the only malignant component present, then it must be deemed by the
pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
(mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
is 45 U/L) (within 7 days prior to enrollment)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to
enrollment) AND
• Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
• Patients enrolling on the standard risk arms must be medically fit to receive protocol
treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
(patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
Exclusion Criteria:
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND
(retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
1000 ng/mL
• Pure immature teratoma COG stage II •IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS
irradiation of brain metastases; (this exception only applies to SR1 patients; any
patients over age 11 with distant metastases to brain [stage IV disease] would be
considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that
contraindicate the use of bleomycin are ineligible for the standard risk arms of the
trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential; (this criteria applies ONLY to patients who will
receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation; (this
criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
patients])
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Hodgkin's Lymphoma, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
Project: Every Child for Younger Patients With Cancer
This study gathers health information for the Project: Every Child for younger patients with
cancer. Gathering health information over time from younger patients with cancer may help
doctors find better methods of treatment and on-going care.
Kenneth Desantes, M.D.
All
up to 25 Years old
N/A
This study is NOT accepting healthy volunteers
NCT02402244
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Inclusion Criteria:
• Enrollment must occur within 6 months of initial disease presentation OR within 6
months of refractory disease, disease progression, disease recurrence, second or
secondary malignancy, or post-mortem
• Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome,
Registry and Future Contact components of APEC14B1 any time after they reach age of
majority
• Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent
or young adult populations are eligible for enrollment as follows:
• All cancer cases with an International Classification of Diseases for Oncology
(ICD-O) histologic behavior code of two "2" (carcinoma in situ) or three "3"
(malignant)
• All neoplastic lesions of the central nervous system regardless of behavior,
i.e., benign, borderline or malignant
• The following other benign/borderline conditions:
• Mesoblastic nephroma
• Teratomas (mature and immature types)
• Myeloproliferative diseases including transient myeloproliferative disease
• Langerhans cell histiocytosis
• Lymphoproliferative diseases
• Desmoid tumors
• Gonadal stromal cell tumors
• Subjects must be =< 25 years of age at time of original diagnosis, except for patients
who are being screened specifically for eligibility onto a COG (or COG participating
National Clinical Trials Network [NCTN]) therapeutic study, for which there is a
higher upper age limit
• All patients or their parents or legally authorized representatives must sign a
written informed consent and agree to participate in at least one component of the
study; parents will be asked to sign a separate consent for their own biospecimen
submission
• If patients or their parents or legally authorized representatives have not
signed the Part A subject consent form at the time of a diagnostic bone marrow
procedure, it is recommended that they initially provide consent for drawing
extra bone marrow using the Consent for Collection of Additional Bone Marrow;
consent using the Part A subject consent form must be provided prior to any other
procedures for eligibility screening or banking under APEC14B1
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Lymphoproliferative Disorder, Malignant Solid Neoplasm, Myeloproliferative Neoplasm, Stromal Neoplasm
Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
This research trial studies biomarkers in tumor tissue samples from patients with newly
diagnosed neuroblastoma or ganglioneuroblastoma. Studying samples of tumor tissue from
patients with cancer in the laboratory may help doctors identify and learn more about
biomarkers related to cancer.
Kenneth Desantes, M.D.
All
up to 30 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00904241
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Inclusion Criteria:
• All newly diagnosed patients with suspected neuroblastoma, suspected
ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype seen at Children's
Oncology Group (COG) institutions are eligible for this study
• There will be no penalty under any circumstances for enrollment of a patient
whose definitive institutional diagnosis, or central review diagnosis, is found
to be a tumor other than neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/
maturing subtype
• Patients may not have received chemotherapy prior to enrollment on ANBL00B1 and
procurement of study-related tissues with the following exception:
• Patients that in the opinion of the treating physician are too ill to undergo
pre-treatment tissue biopsy and require EMERGENT chemotherapy may be enrolled on
ANBL00B1; documentation of the emergent nature of therapy initiation is required
• It is required that a good faith effort (documented by specimen tracking) be made to
submit a neuroblastoma sample (tumor, metastasis, and/or tumor-involved bone marrow)
of sufficient quality for MYCN analysis in the Neuroblastoma Reference Laboratory in
order for any newly diagnosed patient to be enrolled on ANBL00B1; this should be
obtained prior to initiation of therapy
• Exceptions
• In rare cases, patients may be deemed too ill to undergo pre-treatment tissue
biopsy and require EMERGENT therapy; the following eligibility guidelines apply
to these cases:
• For presumed INSS stage 4S patients: Efforts to submit tumor tissue (e.g.,
primary tumor, skin nodule, or metastatic site) within 96 hours of EMERGENT
therapy initiation should be made; however, if the child is deemed too
unstable for such a procedure they may still be enrolled as long as
pre-treatment peripheral blood and serum have been submitted
• For all other INSS stages: tumor tissue should be obtained as soon as
possible within 96 hours of EMERGENT therapy initiation; patients without
tumor tissues submitted within this time-frame are not eligible for
enrollment
• Note: it may not be possible to obtain all necessary tumor biomarkers
for therapy stratification in such cases; if a patient enrolled on
ANBL00B1 undergoes an additional diagnostic procedure within 96 hours
of initiating therapy, additional tumor specimens may be submitted to
obtain biomarkers used for risk classification; the decision to perform
such procedures, and/or submit these specimens, is to be made by the
managing clinicians and should reflect the clinical need to know the
status of such biomarkers
• Patients enrolled on ANBL1232 in Group A (either A1 or A2) will not have a
tumor biopsy or resection upfront; tumor tissue submission is therefore not
required for these patients to enroll on ANBL00B1; a peripheral blood and
serum sample is the only specimen required to be submitted for this group of
patients; should they undergo a biopsy or resection at a later date tumor
can be submitted for biomarker testing at this time
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original
diagnosis are NOT eligible; samples should be submitted as part of the ABTR04B1
protocol
Ganglioneuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Regional Neuroblastoma, Stage 4 Neuroblastoma, Stage 4S Neuroblastoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Neuroblastoma
This research trial studies kidney tumors in younger patients. Collecting and storing samples
of tumor tissue, blood, and urine from patients with cancer to study in the laboratory may
help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify
biomarkers related to cancer.
Kenneth Desantes, M.D.
All
up to 29 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00898365
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Inclusion Criteria:
• Patients with the first occurrence of any tumor of the kidney identified on CT scan or
MRI are eligible for this study; histologic diagnosis is not required prior to
enrollment but is required for all patients once on study
• Eligible tumors include (but are not limited to):
• Nephroblastic tumors
• Nephroblastoma (Wilms' tumor) (favorable histology, anaplasia [diffuse,
focal])
• Nephrogenic rests and nephroblastomatosis
• Cystic nephroma and cystic partially differentiated nephroblastoma
• Metanephric tumors (metanephric adenoma, metanephric adenofibroma,
metanephric stromal tumor)
• Mesoblastic nephroma (cellular, classic, mixed)
• Clear cell sarcoma
• Rhabdoid tumor (any malignant rhabdoid tumor occurring outside the central
nervous system [CNS])
• Renal epithelioid tumors of childhood (papillary renal cell carcinoma, medullary
renal cell carcinoma, renal tumors associated with Xp11.2 translocations,
oncocytic renal neoplasms after neuroblastoma)
• Angiolipoma
• Ossifying renal tumor of infancy
• Patients with the first occurrence of the following tumors are also eligible:
• Extrarenal nephroblastoma or extrarenal neprogenic rests
• Malignant rhabdoid tumor occurring anywhere outside the central nervous system
• Required specimens, reports, forms, and copies of imaging studies must be available or
will become available for submission and the institution must intend on submitting
them as described in the protocol procedures
• For ALL patients, (with exception of bilateral, bilaterally predisposed, multicentric,
or unilateral tumor in solitary kidney planning to enroll without biopsy***), the
following submissions are required:
• A complete set of recut hematoxylin and eosin (H & E) slides (including from
sampled lymph nodes, if patient had upfront nephrectomy)
• * Tissue must be from diagnosis, prior to any renal tumor directed
chemotherapy or radiation (only exception is for presumed favorable
histology Wilms tumor [FHWT] patients discovered to have diffuse anaplastic
Wilms tumor [DAWT] at delayed nephrectomy and plan to enroll at delayed
nephrectomy)
• Representative formalin-fixed paraffin-embedded tissue block or if a block is
unavailable, 10 unstained slides from a representative block of tumor, if
available.
• Tissue must be from diagnosis, prior to any renal tumor directed
chemotherapy or radiation (only exception is for presumed FHWT patients
discovered to have DAWT at delayed nephrectomy and plan to enroll at delayed
nephrectomy)
• Institutional pathology report, Specimen Transmittal Form, and Pre-Treatment
Pathology Checklist
• Copies of images and institutional reports of CT and/or MRI abdomen and pelvis,
and Pre Treatment Imaging Checklist
• Copies of images and institutional report of chest CT for all malignant tumors
• Institutional surgical report(s) and Pre-Treatment Surgical Checklist
• CRFs: Staging Checklist and Metastatic Disease Form (if metastatic disease is
noted on imaging)
• Patients with bilateral, bilaterally predisposed, multicentric, or
unilateral tumor in solitary kidney planning to enroll without biopsy via
imaging only •these patients will not have central review or have a risk
assignment issued, but may contribute to specimen banking for future
research. However, if biopsy is done, tissue must be submitted as for other
renal tumors, and initial risk assignment will require pathology and
surgical rapid central reviews. The Specimen Transmittal Form and Pre
Treatment Pathology Checklist are also needed.
• Please note: if the above required items are not received within 120 days of
study enrollment, the patient will be considered off study
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Protocol JDI2007-01 is an Expanded Access Protocol with therapeutic 131I-MIBG for patients
with neuroblastoma or pheochromocytoma / paraganglioma, who otherwise do not qualify for
available treatments, or where approved treatment is not commercially available.
Kenneth Desantes, M.D.
All
12 Months and over
Pilot/Feasibility
This study is NOT accepting healthy volunteers
NCT01590680
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INCLUSION CRITERIA:
1. Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on tumor
histopathology or elevated urine catecholamines with typical tumor cells in the bone
marrow, OR pheochromocytoma or paraganglioma (less than 12 years of age) not amenable
to curative surgery.
2. Age ≥12 months and able to cooperate with radiation safety restrictions during therapy
period with/without pharmacologic anxiolysis.
3. Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with or without radiation and surgery) or development of progressive
disease at any time (any new lesion or an increase in size of >25% of a pre-existing
lesion). Disease evaluation must be completed within 8 weeks of study entry. If
possible, the disease evaluation should take place subsequent to any intervening
therapy; if intervening therapy does occur, evaluations should be done as clinically
indicated. If patient has received prior treatment with MIBG, they must have a
response or stable disease after the most recent MIBG infusion. Patient may have PD
after showing an initial response to MIBG therapy (at [or around] the day 35-63
post-MIBG therapy evaluation).
4. Stem cells: Patients must have a hematopoietic stem cell product available for
re-infusion after 131I-MIBG treatment at doses of 12 mCi/kg. If no stem cells are
available, then the dose of 131I-MIBG should be <12 mCi/kg.
5. Prior Therapy: Patients may enter this study with or without re-induction therapy for
recurrent tumor. Patients must have fully recovered from the toxic effects of any
prior therapy, meeting the following criteria:
1. At least 2 weeks should have elapsed since any anti-tumor therapy and the patient
must meet certain hematologic criteria.
2. 3 months should have elapsed in the case of completing external beam radiation
for total abdominal, whole lung, total body irradiation (spot irradiation to
skull-based metastases is NOT a contraindication). Patients who receive localized
emergency radiation to sites of life-threatening or function-threatening disease
prior to or immediately after establishment of the definitive diagnosis are not
contraindicated for treatment on this protocol.
3. Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued
a minimum of 24 hours prior to 131I-MIBG therapy.
4. Minimum of six weeks from previous 131I-MIBG therapy.
5. The lifetime cumulative injected activity should be evaluated by the Investigator
on a case-by-case basis with special attention to any recovery from past
131I-MIBG dose(s).
6. For patients who received a stem cell infusion for a previous 131I-MIBG therapy
but do NOT have remaining stored stem cells:
i. If the stem cell reinfusion was protocol driven but not based upon the development
of profound cytopenias (e.g. automatic stem cell reinfusion on Day 14), the patient is
eligible for retreatment with MIBG at a dose <12 mCi/kg at the investigators
discretion; ii. If the stem cell reinfusion was given based upon the development of
profound cytopenias, decisions for re-treatment with 131I-MIBG will require a
case-by-case evaluation by the Investigator.
6. Organ Function:
1. Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit
of normal.
2. Kidney function:
i. Serum Creatinine ≤ 2x upper limit of normal OR ii. 24-hr creatinine clearance OR
GFR ≥ 60 ml/min/1.73m2.
c. Hematologic Criteria: ANC ≥750/uL; Platelets ≥ 50,000/uL without transfusion if
stem cells are not available (ANC ≥ 500 and any platelet count allowed if stem cells
available). Patient must be off myeloid growth factors for at least 24 hours. If the
patient has received prior treatment with MIBG, they may be thrombocytopenic, but
requiring no more than 2 platelet transfusions per week to maintain counts above
20,000/uL. Hemoglobin must be ≥ 10gm/dL (transfusion allowed) regardless of stored
stem cell availability.
d. Normal lung function, as manifested by no dyspnea at rest or exercise intolerance,
no oxygen requirement.
e. No clinically significant cardiac dysfunction.
7. Signed informed consent/assent has been obtained.
EXCLUSION CRITERIA:
1. Patients 12 years and older with iobenguane scan positive, unresectable, locally
advanced or metastatic pheochromocytoma or paraganglioma and marketed product is
available.
2. Patients eligible for the Phase II (OPTIMUM) trial.
3. Patients with disease of any major organ system that would compromise their ability to
withstand therapy. Any significant organ impairment should be discussed with the
Principal Investigator prior to patient entry.
4. Because of the teratogenic potential of the study medications, no patients who are
pregnant or lactating will be allowed. Patients of childbearing potential, who are
sexually active, must practice an effective method of birth control while
participating on this study, to avoid possible damage to the fetus . [e.g.
intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with
intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout
the study].
5. Patients who are on hemodialysis
6. Proteinuria, in the absence of urinary infection, within 4 weeks prior to the planned
treatment date is a relative contraindication to receiving therapy for patients with
pheochromocytoma/paraganglioma. Patients with pheochromocytoma/paraganglioma with any
clinically significant proteinuria must have a 24-hr urine protein determination. If
proteinuria is confirmed as being above the institutional upper limit of normal, the
patient is ineligible for MIBG therapy.
7. Patients with active infections that meet grade 3-4 according to the current version
of the NCI CTCAE.
8. Patients with known MIBG-avid parenchymal brain metastases are not eligible. (Patients
with leptomeningeal or skull-based metastases are eligible.)
Neuroblastoma, Pheochromocytoma, Paraganglioma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites
Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors
This clinical trial studies cancer survivors to identify those who are at increased risk of
developing late-occurring complications after undergoing treatment for childhood cancer. A
patient's genes may affect the risk of developing complications, such as congestive heart
failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer
treatment. Genetic studies may help doctors identify survivors of childhood cancer who are
more likely to develop late complications.
Kenneth Desantes, M.D.
All
up to 99 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00082745
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• ELIGIBILITY CRITERIA •CASES
• Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• No prior history of allogeneic (non-autologous) hematopoietic cell transplant
• Development of one of the following key adverse events at any time following
initiation of cancer therapy:
• Cardiac dysfunction; please note: case enrollment has been closed due to
achievement of target accrual
• Ischemic stroke (IS)
• Subsequent malignant neoplasm (SMN)
• Avascular necrosis (AVN); please note: case enrollment has been closed due to
achievement of target accrual
• Submission of a blood specimen (or in certain cases a saliva specimen) to the
Coordinating Center at the University of Alabama at Birmingham as per the
requirements; please note: if a patient is currently receiving active cancer
treatment, it is preferable to obtain the blood sample at a time when the patient's
white blood cell (WBC) is > 2,000
• Written informed consent from the patient and/or the patient's legally authorized
guardian
• In active follow up by a COG institution; active follow up will be defined as date of
last visit or contact by a COG institution within the past 24 months; any type of
contact, including contact specifically for participation in ALTE03N1, qualifies as
active follow-up; please note: treatment on a COG (or legacy group) therapeutic
protocol for the primary cancer is NOT required
• ELIGIBILITY CRITERIA •CONTROLS
• CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell
transplant
• CONTROLS: No clinical evidence of any of the following key adverse events:
• Cardiac dysfunction (CD); please note: if a patient is currently receiving active
cancer treatment, it is preferable to obtain the blood sample at a time when the
patient's WBC is > 2,000
• Ischemic stroke (IS)
• Avascular necrosis (AVN)
• Subsequent malignant neoplasm (SMN)
• CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to
the Coordinating Center Laboratory at the University of Alabama at Birmingham as per
the requirements
• CONTROLS: Written informed consent from the patient and/or the patient's legally
authorized guardian
• CONTROLS: In active follow up by a COG institution; active follow up will be defined
as date of last visit or contact by a COG institution within the past 24 months; any
type of contact, including contact specifically for participation in ALTE03N1,
qualifies as active follow-up; please note: treatment on a COG (or legacy group)
therapeutic protocol for the primary cancer is NOT required
Childhood Malignant Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia, not otherwise specified, Other Hematopoietic, Ill-Defined Sites, Other
Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ivosidenib works in treating patients
with solid tumors that have spread to other places in the body (advanced), lymphoma, or
histiocytic disorders that have IDH1 genetic alterations (mutations). Ivosidenib may block
the growth of cancer cells that have specific genetic changes in an important signaling
pathway called the IDH pathway.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04195555
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to MATCH to APEC1621K based on the presence of an actionable mutation as
defined in APEC1621SC
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment
• Patients must have a body surface area >= 0.78 m^2 at enrollment
• Patients must be able to swallow intact tablets
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age. Note: Neurologic deficits in patients with CNS tumors must have been
relatively stable for at least 7 days prior to study enrollment. Patients who are
unable to walk because of paralysis, but who are up in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score.
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment. If after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the
last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular Therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam Irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to AG-120 (ivosidenib) or other
IDH1 inhibitors
• For patients with solid tumors without known bone marrow involvement: Peripheral
absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement: Platelet count
>= 100,000/mm^3 (transfusion independent, defined as not receiving platelet
transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood count (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions). These patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment), or
• A serum creatinine based on age/gender (within 7 days prior to enrollment)
• Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6
• Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8
• Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1
• Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2
• Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4
• Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior
to enrollment)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Corrected QT (QTc )interval =< 450 milliseconds (within 7 days prior to enrollment)
• Note: Patients should avoid concomitant medication known or suspected to prolong
QTc interval or cause Torsades de Pointes. Patients who are receiving drugs that
prolong the QTc are eligible if the drug is necessary and no alternatives are
available
• Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE]
version [v]5.0) resulting from prior therapy must be =< grade 2, with the exception of
decreased tendon reflex (DTR). Any grade of DTR is eligible
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent. Assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks
because there is yet no available information regarding human fetal or teratogenic
toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or
females of reproductive potential may not participate unless they have agreed to use
an effective non-hormonal contraceptive method for the duration of study treatment and
for at least 1 month after last dose of AG-120 (ivosidenib). Since AG-120 (ivosidenib)
may decrease concentrations of hormonal contraceptives, hormonal contraceptives are
not considered effective contraception when co-administered with AG-120 (ivosidenib)
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of
corticosteroid for at least 7 days prior to enrollment are not eligible. If used to
modify immune adverse events related to prior therapy, >= 14 days must have elapsed
since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or moderate to
strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to strong
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of
the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed. In addition, patients receiving
sensitive or narrow therapeutic range substrates of CYP3A4 are not eligible
• Patients with a history of progressive multifocal leukoencephalopathy are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Recurrent WHO Grade 2 Glioma, Refractory Ependymoma, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Refractory WHO Grade 2 Glioma, Wilms Tumor
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
This phase II pediatric MATCH trial studies how well tipifarnib works in treating patients
with solid tumors that have recurred or spread to other places in the body (advanced),
lymphoma, or histiocytic disorders, that have a genetic alteration in the gene HRAS.
Tipifarnib may block the growth of cancer cells that have specific genetic changes in a gene
called HRAS and may reduce tumor size.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04284774
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to MATCH to APEC1621M based on the presence of an actionable mutation as
defined in APEC1621SC
• Patients must be >=12 months and =< 21 years of age at the time of study enrollment
• Patients must have a body surface area >= 0.29 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible. Measurable
disease in patients with CNS involvement is defined as any lesion that is at minimum
10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed
tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebral spinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age. Note: Neurologic deficits in patients with CNS tumors must have been
relatively stable for at least 7 days prior to study enrollment. Patients who are
unable to walk because of paralysis, but who are up in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment. If after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy
(42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the
last dose of agent.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radio-pharmaceutical therapy
• Patients must not have received prior exposure to tipifarnib
• For patients with solid tumors without known bone marrow involvement (within 7 days
prior to enrollment):
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• For patients with solid tumors without known bone marrow involvement (within 7 days
prior to enrollment):
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions). These patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: male (0.6), female (0.6)
• 2 to < 6 years: male (0.8), female (0.8)
• 6 to < 10 years: male (1), female (1)
• 10 to < 13 years: male (1.2), female (1.2)
• 13 to < 16 years: male (1.5), female (1.4)
• >= 16 years: male (1.7), female (1.4)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L.) (within 7 days prior
to enrollment)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE]
version [v] 5.0) resulting from prior therapy must be =< grade 2
• Patients must be able to swallow intact tablets or crushed tablets mixed in water,
orange juice, apple juice, tomato juice, ginger ale, applesauce, yogurt, protein
shake, or a dietary supplement drink (such as Ensure). Percutaneous endoscopic
gastrostomy (PEG)-tube or nasogastric tube administration is permitted
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent. Assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of
fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests
must be obtained in girls who are post-menarchal. Males or females of reproductive
potential may not participate unless they have agreed to use two effective
contraceptive methods for the duration of study treatment. Both female subjects and
male subjects with female partners of child-bearing potential must agree to use a
highly effective method of contraception for 2 weeks prior to protocol therapy,
during, and at least 4 weeks after last dose of tipifarnib. In addition, since
tipifarnib could induce toxicity of male reproductive organs and cause impairment of
fertility, sperm cryopreservation should be recommended for male subjects wishing to
preserve their fertility following tipifarnib treatment
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of
corticosteroid for at least 7 days prior to enrollment are not eligible. If used to
modify immune adverse events related to prior therapy, >= 14 days must have elapsed
since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or inhibitors of
CYP3A4/5 or UGT are not eligible. Strong inducers or inhibitors of CYP3A4/5 or UGT
should be avoided from 14 days prior to the 1st dose of tipifarnib to the end of the
study. In addition, patients receiving agents that are sensitive or narrow therapeutic
range substrates of CYP3A4/5 are not eligible. Note: CYP3A4/5 inducing anti-epileptic
drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients with known hypersensitivity to tipifarnib or any components of the tablet are
not eligible
• Patients with hypersensitivity to imidazoles, such as clotrimazole, ketoconazole,
miconazole and others in this drug class are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Malignant Solid Neoplasm, Recurrent Adrenal Gland Pheochromocytoma, Recurrent Ectomesenchymoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Kidney Wilms Tumor, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Melanoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Rhabdoid Tumor, Recurrent Rhabdoid Tumor of the Kidney, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Recurrent Thyroid Gland Carcinoma, Recurrent WHO Grade 2 Glioma, Refractory Adrenal Gland Pheochromocytoma, Refractory Ependymoma, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Melanoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Refractory Rhabdoid Tumor of the Kidney, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Refractory Thyroid Gland Carcinoma, Refractory WHO Grade 2 Glioma
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric
patients with high-risk neuroblastoma.
Kenneth Desantes, M.D.
All
Not specified
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04023331
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Participant is able and willing to provide informed consent (≥18 years), or informed
consent is obtained by the parent or legal guardian for minor participants, with the
minor providing age appropriate assent, according to local law and regulations;
2. Life expectancy ≥ 12 weeks;
3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has
relapsed or progressed to high-risk, with failure to achieve complete response with
standard therapy (defined as at least 4 cycles of aggressive multi-drug induction
chemotherapy with or without radiation and surgery, or according to a standard
high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to
receive standard treatment OR who are intolerant to standard treatment;
4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the
Investigator or treating Sub-Investigator;
5. Adequate liver function as defined by the following laboratory values obtained within
28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
6. Adequate renal function;
7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet
count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
8. Karnofsky or Lansky performance status ≥50;
9. All participants must have a hematopoietic stem cell product available (minimum CD34+
cell dose is ≥2 x 10 6 cells/kg);
10. Sexually active participants of reproductive potential must practice an effective
method of birth control while participating on this study, to avoid possible damage to
the fetus. Abstinence is considered acceptable;
11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than
that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
1. Participants with disease of any major organ system that would compromise their
ability to tolerate therapy, as deemed by the Investigator or treating
Sub-Investigator;
2. Any other active malignancy, or a history of prior malignancy within the past 3 years;
3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance,
oxygen requirement, clinically significant cardiac dysfunction;
4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or
radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the
administration of 64Cu-SARTATE;
6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney
within 12 months prior to the administration of 64Cu-SARTATE;
7. Administration of any investigational agents within 21 days prior to administration of
64Cu-SARTATE;
8. Treatment with long acting somatostatin analogues (administered within 28 days prior
to the administration of 64Cu-SARTATE), or short acting somatostatin analogues
(administered within 24 hours prior to the administration of 64Cu-SARTATE);
9. Known sensitivity or allergy to somatostatin analogues;
10. Previous peptide receptor radionuclide therapy (PRRT);
11. Female participants who are pregnant or lactating;
12. Participants who are on hemodialysis;
13. QTc interval ≥ 0.45 seconds as measured by Screening ECG;
14. Participants with uncontrolled infection(s);
15. Any medical condition which the Investigator feels may interfere with the procedures
or evaluations of the study;
16. Participants 12 months and younger will be excluded from cohorts where the planned
single or cumulative administered activity is modelled to deliver a radiation dose to
the marrow that exceeds 2 Gy.
Neuroblastoma, Relapsed Neuroblastoma, Refractory Neuroblastoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
This phase II pediatric MATCH treatment trial studies how well selpercatinib works in
treating patients with solid tumors that may have spread from where they first started to
nearby tissue, lymph nodes, or distant parts of the body (advanced), lymphomas, or
histiocytic disorders that have activating RET gene alterations. Selpercatinib may block the
growth of cancer cells that have specific genetic changes in an important signaling pathway
(called the RET pathway) and may reduce tumor size.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04320888
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to MATCH to APEC1621N based on the presence of an actionable mutation
• Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible. Measurable
disease in patients with CNS involvement is defined as any lesion that is at minimum
10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebral spinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age. Note: Neurologic deficits in patients with CNS tumors must have been
relatively stable for at least 7 days prior to study enrollment. Patients who are
unable to walk because of paralysis, but who are up in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment. If after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy
(42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last
dose of agent.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to selpercatinib (LOXO-292) or
other specific RET inhibitors
• For patients with solid tumors without known bone marrow involvement (within 7 days
prior to enrollment):
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• For patients with solid tumors without known bone marrow involvement (within 7 days
prior to enrollment):
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions). These patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on
age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: male (0.6), female (0.6)
• 2 to < 6 years: male (0.8), female (0.8)
• 6 to < 10 years: male (1), female (1)
• 10 to < 13 years: male (1.2), female (1.2)
• 13 to < 16 years: male (1.5), female (1.4)
• >= 16 years: male (1.7), female (1.4)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L. (within 7 days prior to enrollment) (For the purpose of this study, the ULN for
SGPT is 45 U/L.)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Corrected QT (QTc) interval =< 480 milliseconds (within 7 days prior to enrollment)
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent. Assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of
fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests
must be obtained in girls who are post-menarchal. Males or females of reproductive
potential may not participate unless they have agreed to use two (2) highly effective
contraceptive method for the duration of study treatment and for at least 2 weeks
after the last dose of selpercatinib (LOXO-292). Male study participants are to
refrain from sperm donation during treatment and for 2 weeks after the last dose of
selpercatinib (LOXO-292)
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of
corticosteroid for at least 7 days prior to enrollment are not eligible. If used to
modify immune adverse events related to prior therapy, >= 14 days must have elapsed
since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are moderate or strong inducers or
inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should
be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4
inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a
stable dose, are allowed
• Proton pump inhibitors (PPIs), H2 receptor antagonists and antacids: Concomitant use
of PPIs during selpercatinib (LOXO-292) therapy should be avoided if feasible. If
co-administration of selpercatinib and PPI is necessary, administer selpercatinib with
a meal. If H2 receptor antagonist is necessary, administer selpercatinib 2 hours
before or 10 hours after H2 receptor antagonist administration. If antacid use is
necessary, administer selpercatinib 2 or more hours before or 2 or more hours after
antacid administration
• Patients who have major surgery within 14 days prior to cycle 1 day 1 (C1D1) are not
eligible. (Central line placement or subcutaneous port placement is not considered
major surgery)
• Patients with known clinically significant active malabsorption syndrome or other
condition likely to affect gastrointestinal absorption of selpercatinib (LOXO-292) are
excluded
• Patients with known hypersensitivity to any of the components of the investigational
agent, LOXO 292 are excluded
• Patients with uncontrolled hypertension are excluded
• Patients with uncontrolled symptomatic hyperthyroidism and hypothyroidism (i.e. the
patient required a modification to current thyroid medication in 7 days prior to
enrollment) are excluded
• Patients with uncontrolled symptomatic hypercalcemia and hypocalcemia are excluded
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Hematopoietic and Lymphoid System Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Histiocytic and Dendritic Cell Neoplasm, Recurrent Langerhans Cell Histiocytosis, Recurrent Lymphoma, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Recurrent WHO Grade 2 Glioma, Refractory Ependymoma, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Histiocytic and Dendritic Cell Neoplasm, Refractory Langerhans Cell Histiocytosis, Refractory Lymphoma, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Refractory WHO Grade 2 Glioma, Wilms Tumor
Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma (MiniVan)
Neuroblastoma, the most common extra-cranial solid tumour in children, remains one of the
major challenges in paediatric oncology. A promising way to further improve outcome in this
disease appears to be the development of adjuvant therapeutic strategies. In this research
the anti-GD2 antibody, which is a standard treatment, is to be combined with 131-l
Metaiodobenzylguanidine (mlBG) and anti-Programmed Cell Death Protein 1 (anti-PD1) antibody
Nivolumab - the investigated drugs - with the aim of generating sustained anti-neuroblastoma
immunity. In particular it will be determined the safety and tolerability of the novel
combination as well as documented any evidence of efficacy in paediatric patients with
relapsed and refractory high risk neuroblastoma.
This study is sponsored by the University Hospital Southampton and will take place in 4
hospitals in the United Kingdom, Germany and USA. The estimated duration of the study is 2
years, starting in December 2016.
This is an "adaptive study". Such design uses accumulating of data from the ongoing trial to
modify aspects of the study (e.g. duration, number of treatments) without undermining its
validity or integrity. There will be 3 cohorts of patients. As safety of Nivolumab is well
established, Cohort 1 will assess its safety and tolerability in combination with 131-l mlBG.
Cohort 2 will then add anti-GD2 to the drug combination, assessing safety and tolerability.
Cohort 3 will escalate all 3 agents to the full 100% dose level to assure safety for expanded
analyses of clinical and laboratory data at that dose level.
Patients will initially be recruited into Cohort 1. Patients must have completed at least 12
weeks of trial treatment without reaching a Dose Limiting Toxicity before a patient can be
recruited to the next cohort.
A minimum of 3 evaluable patients will be treated in cohorts 1-3. Assuming the full dose
combination therapy (cohort) is tolerable, 15 evaluable patients will be treated.
Kenneth Desantes, M.D.
All
1 Year to 99 Years old
Phase 1
This study is also accepting healthy volunteers
NCT02914405
Show full eligibility criteria
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Inclusion Criteria:
• At study entry patients must be > 1 year
• Relapsed or refractory high risk neuroblastoma (as defined by International
Neuroblastoma Risk Group (INRG) criteria)
• MIBG avid disease on imaging within 4 weeks to study entry.
• ≥ 3 months since any myeloablative chemotherapy / stem cell rescue
• ≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives
since last dose of any monoclonal antibody therapy.
• Patients must have a performance status greater or equal 60% (Lansky Score or
Karnofsky)
• Estimated life expectancy ≥ 12 weeks
• Adequate bone marrow function: Absolute Neutrophil Count (ANC) >1.0 x 10/L, platelets,
20 x 10/L and haemoglobin > 8.0 g/dL.
• Adequate renal function: serum creatinine <1.5 mg/dL or a estimated creatinine
clearance or radioisotope Glomerular Filtration Rate Study (GFR) of > 60
mL/minute/1.73m2.
• Adequate cardiac function: shortening fraction of 28 % by echocardiogram.
• Adequate hepatic function: Alanine transaminase (ALT) or Aspartate transaminase (AST)
< 5 x ULN and a total bilirubin < 1.5 x Upper Limit of Normal (ULN)
• Adequate lung function: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital
Capacity (FVC) >60% of the predicted by pulmonary function tests. Children unable to
do Pulmonary Function Tests (PFTs) should have no dyspnea at rest and a pulse oximetry
>94% on room air.
• Adequate pancreatic function: serum lipase < 1.5 x upper limit normal
• Patients may have had prior Central Nervous System (CNS) metastasis at point of entry
to study, but patients with mIBG avid parenchymal brain lesions will be excluded. All
CNS disease must be treated and stable prior for at least 4 weeks prior to starting
trial 131-I mIBG therapy (see section 4). Patients with extra-axial disease (e.g.
skull (bone) metastasis that do not invade the dura) may be enrolled providing there
is no evidence of brain oedema.
• Patients must consent to the placement of a central venous line, if one has not
already been placed.
• Patients must have no immediate requirements for palliative chemotherapy, radiotherapy
or surgery.
• Females of childbearing potential must have a negative pregnancy test. Patients of
childbearing potential must agree to use an effective birth control method. Female
patients who are lactating must agree to stop breast-feeding.
• Patients with seizure disorders may be enrolled if seizures are well controlled.
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional and national requirements for clinical trials must be met.
• Expression of PD-L1 by tumour is not a pre-requisite
• Parents or carers willing and able to comply with radiation safety measures needed for
131-I mIBG administration.
• Patient must be judged capable of tolerating isolation procedures associated with
131-I-mIBG therapy
Exclusion Criteria
• Patients who have previously received ch14.18 (CHO or SP2/0) will not be excluded
unless they have had severe or life threatening toxicity necessitating withdrawal of
treatment previously or if they have a strong/neutralizing Human Antichimeric Antibody
(HACA) (≥ 10 μg/ml)
• Patients who have had previous 131-I mIBG therapy will not be excluded
• Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting
antibodies will be excluded from the study
• Previous allogeneic stem cell transplant or solid organ transplant
• Patients should be excluded if they have an active, known or suspected autoimmune
disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes
mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger
• Patients receiving systemic corticosteroids (other than physiological replacement) or
other immunosuppressive agents within 14 days prior to study entry
• Unable to maintain platelets ≥ 50 x 109/l without transfusion
• HIV or Hepatitis B or C infection
• Patients with significant intercurrent illnesses and/or any of the following:
• Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm
disturbance.
• Patients with significant psychiatric disabilities or uncontrolled seizure
disorders.
• Patients with active infections.
• Patients with a clinically significant neurologic deficit or objective peripheral
neuropathy (Grade >2) are ineligible.
• Patients with clinically significant, symptomatic, pleural effusions.
• Patients who require, or are likely to require, corticosteroid or other
immunosuppressive drugs.
Neuroblastoma, Stomach, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Other Skin, Other Male Genital, Kidney, Eye and Orbit, Thyroid, Other Endocrine System, Other Hematopoietic, Ill-Defined Sites, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with
newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology
Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such
as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan)
and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work
in different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help doctors find out
what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and
standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen
ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with
3 or more drugs for the initial WT).
Kenneth Desantes, M.D.
All
up to 30 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04322318
Show full eligibility criteria
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Inclusion Criteria:
• Patients with newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if
anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a
delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed
nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an
eligibility requirement for patients with relapsed favorable histology Wilms tumor.
• Patients must be =< 30 years old at study enrollment
• Patients with the following diagnoses are eligible for this study:
• Newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor as confirmed by
central review
• Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must
have previously achieved remission for their initial FHWT diagnosis to be
eligible for this study. The relapse risk groups are defined as follows,
regardless of radiation therapy:
• Standard-Risk relapse: Patients who received two chemotherapy agents for
frontline therapy; primarily actinomycin D and vincristine
• High-Risk relapse: Patients who received three chemotherapy agents for
frontline therapy; primarily vincristine, actinomycin D and doxorubicin or
vincristine, actinomycin D and irinotecan
• Very High-Risk relapse: Patients who received four or more chemotherapy
agents as part of initial therapy; primarily regimen M or its variations
• Patients with newly diagnosed DAWT must have had histologic verification of the
malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but
not required
• Note: For relapsed FHWT patients, an institutional pathology report confirming
favorable histology Wilms tumor (from relapse, if available, or from original
diagnosis) must be available for upload prior to initiation of protocol therapy
• Patients with newly diagnosed Stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure
that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or
delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior
therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse
anaplastic Wilms tumor at subsequent review of the initial biopsy
• Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least
1 lymph node sampled prior to study enrollment
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have
had no prior systemic therapy, except in the following situations:
• Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks
of pre nephrectomy chemotherapy for what was originally presumed to be favorable
histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms
tumor at delayed nephrectomy
• Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of
chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for
presumed favorable histology Wilms tumor based on institutional review, but
subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2
initial risk assignment results (if available per current version of AREN03B2)
• Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an
emergent basis and within allowed timing as described
• Note: Patients who received prior therapy for presumed favorable histology Wilms
tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must
begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who
received emergency radiation to preserve organ function are eligible as noted.
Patients who received radiation as part of standard of care for presumed newly
diagnosed favorable histology Wilms tumor, along with chemotherapy as noted
above, prior to identification of diffuse anaplasia, are also eligible
• Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior
chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In
addition, patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study
• Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative
RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >=
50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone
marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who
received emergency radiation to preserve organ function are eligible and do not
need to washout with the above criteria
• Patients may not be receiving any other investigational agents (within 4 weeks prior
to study enrollment)
• Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to
enrollment)
• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior
to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed
within 7 days prior to enrollment)
• Patients with high-risk or very high-risk relapsed FHWT who will be treated with
regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or
radioisotope glomerular filtration rate (GFR) and meet the following requirement:
• Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within
7 days prior to enrollment)
• Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be
treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR
(meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum
creatinine as per the following table:
• Age: Maximum Serum Creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 0.6 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =<
ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases
(performed within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram (obtained within 21 days prior to enrollment and start of
protocol therapy)
Exclusion Criteria:
• Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
• Patients with any uncontrolled, intercurrent illness including, but not limited to,
ongoing or active infection, or symptomatic congestive heart failure (defined as grade
2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0)
• Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk
FHWT initially observed without chemotherapy) or received only one chemotherapy agent
for frontline therapy
• For patients with high-risk or very high-risk relapsed FHWT:
• Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16
mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
• For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use of St. John's wort, which cannot be stopped prior to the start of
trial treatment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Kidney, Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor
Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors
This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety,
tolerability, MTD PK, and PD of TJ033721 in subjects with advanced or metastatic solid
tumors.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04900818
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Inclusion Criteria:
• Subjects with advanced or metastatic solid tumor in subjects whose disease has
progressed despite standard therapy, or who has no further standard therapy, or who is
unsuitable for available standard treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate
organ function
• Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding
combined positive score (CPS)
For dose expansion study only:
• Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, and
esophageal adenocarcinoma without further standard therapy or unsuitable for available
standard treatment options.
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay
Exclusion Criteria
• Prior exposure to CLDN18.2 -targeted therapy
• Prior exposure to 4-1BB agonists
• Second malignancy within the last 3 years with the exception of cutaneous squamous
cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ
• Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
• Unstable/active ulcer or digestive tract bleeding within 6 weeks
• Active autoimmune disease requiring systemic treatment within the past 2 years
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or
pneumonitis requiring treatment
• Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously
treated brain metastases may participate provided they are clinically stable and
without requirement of steroid treatment for at least 14 days prior to first dose of
study treatment;
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure,
severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart
failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism,
pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein
thrombosis, or coronary artery bypass grafting (CABG) in the previous 6 months
• Diagnosis of immunodeficiency such as known active HIV
• Any active infection requiring parenteral treatment
Solid Tumor, Advanced Cancer, Metastatic Cancer, Gastric Cancer, Gastroesophageal Junction Carcinoma, Esophageal Adenocarcinoma, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
A Safety Study of SEA-TGT (SGN-TGT) in Advanced Cancer
This trial will look at a drug called SEA-TGT (also known as SGN-TGT) to find out whether it
is safe for patients with solid tumors and lymphomas. It will study SEA-TGT to find out what
its side effects are. A side effect is anything the drug does besides treating cancer. It
will also study whether SEA-TGT works to treat solid tumors and lymphomas.
The study will have four parts. Part A of the study will find out how much SEA-TGT should be
given to patients. Part B will use the dose found in Part A to find out how safe SEA-TGT is
and if it works to treat solid tumors and lymphomas. Part C will study how well SEA-TGT with
sasanlimab works to treat solid tumors. Part D will study how well SEA-TGT with brentuximab
vedotin works to treat classical Hodgkin lymphoma (cHL).
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04254107
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Monotherapy Inclusion Criteria (Parts A and B)
• Histologically- or cytologically-confirmed advanced or metastatic malignancy, defined
as:
• One of the following tumor types:
• Unresectable locally-advanced or metastatic non-small cell lung cancer
(NSCLC), gastric/gastroesophageal (GE) junction carcinoma, cutaneous
melanoma, head and neck squamous cell carcinoma (HNSCC), bladder cancer,
cervical cancer, ovarian cancer, or triple negative breast cancer (TNBC)
• Lymphomas, including:
• cHL
• Diffuse large B-cell lymphoma (DLBCL)
• Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)
• Lymphoma: Participants should have disease progression on or after treatment
with standard therapies expected to provide benefit in the judgement of the
investigator.
• cHL: Participants must have received at least 3 prior systemic
therapies. Participants should have had disease recurrence or
progression following brentuximab vedotin therapy or have been
ineligible to receive brentuximab vedotin. Participants who have not
received autologous stem cell transplant (SCT) must have refused or
been deemed ineligible. Participants should have received or not be
eligible to have received an anti-PD-1 agent.
• DLBCL: Participants must have received at least 2 prior systemic
chemo-immunotherapy regimens, including an anti-CD20 agent and
combination chemotherapy. Unless clinically contraindicated,
participants should have had disease that has relapsed after or be
refractory to intensive salvage chemotherapy, including autologous SCT.
• PTCL-NOS: Participants must have had at least 1 prior systemic therapy.
Participants must have received or have been ineligible to receive the
combination of cyclophosphamide, doxorubicin, vincristine, and
prednisone (CHOP) or CHOP-like therapy. Participants with CD30-positive
disease must have received or be ineligible to receive brentuximab
vedotin. Participants must have also received intensive salvage therapy
(defined as combination chemotherapy ± autologous SCT) unless they
refused or were deemed ineligible.
• Measurable disease defined as:
• Solid tumors: Measurable disease according to RECIST V1.1
• Lymphomas: Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography
(PET) and measurable disease of ≥15 mm in the greatest transverse diameter by
computed tomography (CT) scan, as assessed by the site radiologist.
• A representative archival tumor tissue sample should be available as follows:
Participants must provide archived tumor tissue, if available, from the most recent
biopsy (less than or equal to [≤] 12 months from screening). If archived tissue is not
available, a fresh baseline tumor biopsy will be requested for any participant
enrolled in Part B whose tumors are considered accessible and appropriate in the
opinion of the investigator.
• ECOG Performance Status score of 0 or 1
Combination Inclusion Criteria (Part C)
• ECOG Performance Status score of 0 or 1
• NSCLC: histological or cytological confirmed metastatic disease. Participants must
have received no prior anti-PD-1/PD-L1 therapy allowed.
• HNSCC: histological or cytological confirmed metastatic disease. Participants must
have received no prior exposure to anti-PD-1/PD-L1 therapy.
• Cutaneous Melanoma: histological or cytological confirmed metastatic disease.
Participants must not have received anti-PD-1/PD-L1 targeted therapy.
• Measurable disease by CT or magnetic resonance imaging (MRI) as defined by RECIST V1.1
• Participants must provide archival tumor tissue from the most recent biopsy (≤12
months from screening). If archival tissue is not available, a fresh baseline tumor
biopsy that has not been previously irradiated is required for any participant whose
tumors are considered accessible and appropriate in the opinion of the investigator.
Combination Inclusion Criteria (Part D)
• Histologically- or cytologically-confirmed advanced stage cHL
• cHL patients that have failed standard of care for R/R disease including prior
treatment with BV.
• FDG PET emission tomography avid and bidimensional measurable disease of at least 1.5
cm in longest axis as documented by radiographic technique
• ECOG performance status of ≤ 2
• Participants are required to have tumor tissue, if available, from the most recent
biopsy (≤12 months from screening) prior to start of study treatment. If archival
tissue is not available, a fresh screening tumor biopsy is required for any
participant whose tumors are considered accessible and appropriate in the opinion of
the investigator.
Monotherapy Exclusion Criteria (Parts A and B)
• History of another malignancy within 2 years before the first dose of study drug, or
any evidence of residual disease from a previously diagnosed malignancy. Exceptions
are malignancies with a negligible risk of metastasis or death.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not
been completed before the first dose of study drug within the timeframe as follows:
• Chemotherapy, small molecule inhibitors, radiation, and/or other investigational
anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
• Palliative radiotherapy (≤2 weeks of radiotherapy to non-central nervous
system [CNS] disease): ≤7 days prior to start of SEA-TGT
• Immune-checkpoint inhibitors: 4 weeks
• Monoclonal antibodies, antibody-drug conjugates (ADC), or radioimmunoconjugates:
4 weeks (2 weeks with documented disease progression)
• T-cell or other cell-based therapies: 12 weeks
• Known CNS metastases
• Participants with a history of CNS metastases are allowed if they have undergone
treatment for the CNS disease, symptoms have resolved, and steroids have been
discontinued.
• Leptomeningeal involvement by malignant disease is excluded regardless of prior
treatment.
• Previous allogeneic stem cell transplant (SCT). Participants with prior autologous SCT
may be eligible if they are >100 days from autologous SCT and fulfill all other
inclusion criteria.
• Prior use of any anti-TIGIT mAb.
• Participants with a condition requiring systemic treatment with either corticosteroids
(greater than [>]10 mg daily prednisone or equivalent) or other immunosuppressive
medications within 14 days of enrollment. Inhaled or topical steroids and adrenal
replacement steroid doses >10 mg daily prednisone or equivalents are permitted in the
absence of active immune disease.
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT
Combination Exclusion Criteria (Part C)
• History of another malignancy within 2 years before the first dose of study drug, or
any evidence of residual disease from a previously diagnosed malignancy. Exceptions
are malignancies with a negligible risk of metastasis or death.
• Active, non-infectious pneumonitis, pulmonary fibrosis, or known history of immune
mediated pneumonitis.
• Previous therapy with an anti-PD-1 or anti-PD-L1 inhibitor.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not
been completed before the first dose of study drug within the timeframe as follows:
• Chemotherapy, small molecule inhibitors, radiation, and/or other investigational
anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
• Palliative radiotherapy (≤2 weeks of radiotherapy to non-CNS disease): ≤7
days prior to start of SEA-TGT.
• Immune-checkpoint inhibitors: 4 weeks
• Monoclonal antibodies, ADC, or radioimmunoconjugates: 4 weeks (2 weeks with
documented disease progression)
• T-cell or other cell-based therapies: 12 weeks
• Known active CNS metastases.
• Participants with a history of CNS metastases are allowed if they have undergone
treatment for the CNS disease, symptoms have resolved, and steroids have been
discontinued.
• Leptomeningeal involvement by malignant disease is excluded regardless of prior
treatment.
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT
or sasanlimab
• Participants with active known or suspected autoimmune disease or significant
autoimmune-related toxicity from prior immuno-oncology-based therapy (prior autoimmune
colitis, pneumonitis, transaminitis); Participants with vitiligo, controlled type 1
diabetes mellitus, residual hypothyroidism requiring hormone replacement, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.
• History of interstitial lung disease
• Participants with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone or equivalent) or other immunosuppressive medications within
14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid
doses >10 mg daily prednisone or equivalents are permitted in the absence of active
immune disease.
• Prior use of any anti-TIGIT mAb
Combination Exclusion Criteria (Part D)
• History of another malignancy within 2 years before the first dose of study drug, or
any evidence of residual disease from a previously diagnosed malignancy. Exceptions
are malignancies with a negligible risk of metastasis or death.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not
been completed before the first dose of study drug within the timeframe as follows:
• Chemotherapy, small molecule inhibitors, radiation, and/or other investigational
anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
• Palliative radiotherapy (≤2 weeks of radiotherapy to CNS disease): ≤7 days
prior to start of SEA-TGT
• Immune-checkpoint inhibitors: 4 weeks
• Monoclonal antibodies, ADC (except brentuximab vedotin), or
radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)
• T-cell or other cell-based therapies: 12 weeks
• Known active CNS involvement by lymphoma
• Previous allogeneic SCT. Participants with prior autologous SCT may be eligible if
they are >100 days from autologous SCT and fulfill all other inclusion criteria.
• Prior use of any anti-TIGIT mAb.
• Participants with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone or equivalent) or other immunosuppressive medications within
14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid
doses >10 mg daily prednisone or equivalents are permitted in the absence of active
immune disease.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Non-small Cell Lung Cancer, Gastric Carcinoma, Gastroesophageal Junction Carcinoma, Classical Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma, Peripheral T-cell Lymphoma, Cutaneous Melanoma, Head and Neck Squamous Cell Carcinoma, Bladder Cancer, Ovarian Cancer, Triple Negative Breast Cancer, Cervical Cancer
Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
The purpose of this study is to find out whether the study drug, LY3537982, is safe and
effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must
have already received or were not able to tolerate the standard of care, except for specific
groups who have not had cancer treatment. The study will last up to approximately 4 years.
Dustin Deming, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04956640
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Inclusion Criteria:
• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or
circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally
advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any
significant ongoing adverse events (AEs).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.
• For some parts of the study, (i.e., one of the two arms with LY3537982 in combination
with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab,
pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage
IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic
setting and not suitable for curative intent radical surgery or radiation therapy.
Previously untreated patients who received adjuvant and neoadjuvant therapy are
eligible if the last dose of the systemic treatment was completed at least 6 months
prior to enrollment. For untreated patients in the arm with LY3537982 in combination
with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated
within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in
combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of
the drugs other than LY3537982 may be initiated within 21 days prior to enrollment.
Exclusion Criteria:
• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an
additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or
carcinomatous meningitis. Patients with treated CNS metastases are eligible for this
study if they are not currently receiving corticosteroids in excess of 10 milligrams
(mg) per day prednisone/prednisolone (or equivalent) and their disease is asymptomatic
and radiographically stable for at least 30 days. This only applies to some parts of
the study.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in
certain scenarios where such prior therapy is allowed as per protocol.
• Patients treated with drugs known to be strong inhibitors or inducers of cytochrome
P450 (CYP)3A may be excluded.
• The following patients will be excluded from some parts of the study:
• Experienced certain serious side effects with prior immunotherapy.
• Have an active autoimmune disease that has required systemic anti-autoimmune
treatment in the past 2 years.
• Have received a live vaccine within 30 days prior to the first dose of study
drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 180 days after the last dose of study
medication.
• Known allergic reaction against any of the components of the study treatments.
Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplams, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
This phase III trial compares the safety and effect of adding vinorelbine to vincristine,
dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk
rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after
treatment or spread to other parts of the body. This study will also examine if adding
maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the
cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in
a class of medications called vinca alkaloids. They work by stopping cancer cells from
growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only
used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and
may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the
body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are
chemotherapy medications that work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or
for the rest of patient's life.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04994132
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Inclusion Criteria:
• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based
upon institutional histopathologic classification are eligible to enroll on the study
based upon stage, group, and age, as below. FOXO1 fusion status must be determined by
week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include
those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as
ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the
2020 World Health Organization (WHO) Classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant).
Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in
the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy
based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on
hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow
involvement on H&E, patients with bone marrow involvement detected ONLY by flow
cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in
situ hybridization (FISH), or immunohistochemistry will NOT be considered to have
clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be
performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within
7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must
be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated
with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is
allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor
(i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation
therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are
eligible, provided they are consented to ARST2031 prior to administration of
radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for
non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must
discontinue chemotherapy for non-malignant conditions prior to starting protocol
therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients
must not have received drugs that are moderate to strong CYP3A4 inhibitors and
inducers within 7 days prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma
Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine
the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as
monotherapy and in combination with Zimberelimab in participants with advanced solid tumors.
This study will be conducted in 5 parts (Parts A, B, and E: monotherapy, Parts C and D:
combination therapy), in participants with advanced solid tumors who have received, been
intolerant to, or been ineligible for all treatments known to confer clinical benefit or in
participants with select solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05007782
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Key
Inclusion Criteria:
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select
indications who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit or whose disease is indicated for
anti-PD-(L)1 monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatment known to confer clinical benefit.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for
individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D and E.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in
heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D and E: Must provide pre-treatment adequate tumor tissue sample
prior to enrolment.
• Part B: Must have fresh pre-treatment and on-treatment biopsy for biomarker
analysis.
Key
Exclusion Criteria:
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol
specified time prior to initiation of study including: immunotherapy or biologic
therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14
days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21
days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell
transplantation. Exception: prior corneal transplant without requirement for systemic
immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected
carcinoma in situ, localized prostate cancer, or superficial bladder cancer after
undergoing potentially curative therapy with no evidence of disease. Individuals with
other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe
immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic
treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis
(excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not
controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human
immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced Solid Tumor
Study of DF1001 in Patients With Advanced Solid Tumors
DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express human epidermal growth factor receptor 2 (HER2). Two combination
therapy cohorts will be opened for enrollment, DF1001 + nivolumab and DF1001 + Nab
paclitaxel. The second phase will include a dose expansion using the best dose selected from
the first phase of the study. Multiple cohorts will be opened with eligible patients having
either selected solid tumors, or solid tumors expressing high levels of HER2.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04143711
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography
(preferred) or multigated acquisition (MUGA) scan.
5. Adequate hematological function.
6. Adequate hepatic function.
7. Adequate renal function.
8. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
Dose Escalation
1. Evidence of objective disease, but participation does not require a measurable lesion.
2. Locally advanced or metastatic solid tumors, for which no standard therapy exists, or
standard therapy has failed.
3. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
"3+3" Nivolumab Combination Cohort
1. Eligible to receive nivolumab per its label for a malignancy of epithelial origin; or
2. Have no standard therapy available, or standard therapy has failed, and must not have
received nivolumab prior to joining the study.
3. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
"3+3" Nab paclitaxel Combination Cohort
1. Patients must be eligible for treatment with nab-paclitaxel per its label, which
includes metastatic breast cancer, after failure of combination chemotherapy for
metastatic disease or relapse within 6 months of adjuvant chemotherapy. In this case,
additional inclusion criteria include also no exposure to taxanes in the last 6
months, OR
2. Patients whose tumor has no standard therapy or for which standard therapy has failed.
In this case, patients should also not have been treated with a taxane over the last 6
months, OR
3. First line advanced (unresectable/recurrent/metastatic) TNBC
4. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy
Inclusion Criteria:
Safety/PK/PD Expansion Cohorts (Monotherapy and Combination Therapy)
1. Fresh tumor biopsy must be obtained during the screening window.
2. HER2 expression by immunohistochemistry (IHC).
3. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
Inclusion Criteria:
Urothelial Bladder Cancer Expansion Cohort(s)
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically or cytologically documented locally advanced or metastatic transitional
cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial,
urethra).
3. Patients must have radiographic disease progression after their last line of therapy.
4. Patients must have received a platinum containing chemotherapy and an anti PD-1 or
anti PD-L1 for the treatment of urothelial bladder cancer.
5. Patients must have experienced radiographic progression of disease during treatment
with PD-1/PD-L1 containing therapy.
6. Patients must have at least 1+ expression of HER2 by IHC.
7. For patients that will receive DF1001 in combination with nivolumab: progression while
under anti PD-(L)1 must have occurred within 6 months of patient inclusion
8. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Breast Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Absence of erbb2 amplification by ISH and/or HER2 IHC of 0, 1+, or 2+. If Herceptest
score is 0, HER2 must be detected by IHC on at least 1+ of the tumor cells.
4. Patient must have progressed after one line of systemic chemotherapy. Treatment with a
trastuzumab-containing ADC will be considered as a line of chemotherapy.
5. Patients must have progressed (radiographically) after their last line of systemic
therapy.
6. HR-positive patients must have received hormone therapy and have progressed while
receiving hormone therapy.
7. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Breast Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Erbb2 amplification by ISH and/or HER2 IHC of 3+, or 2+. If Herceptest score is 2+,
ISH results should demonstrate erbb2 amplification.
4. Patient must have received trastuzumab, pertuzumab, and a HER2-targeting ADC. Other
anti HER2 lines of therapy are acceptable.
5. Patient must have progressed after one line of systemic chemotherapy.
6. HR-positive patients must have received hormone therapy and have progressed while
receiving hormone therapy.
7. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Basket erbb2 amplified Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Patients with any solid tumor except breast cancer, gastric cancer, or esophageal
cancer that have progressed after an HER2 targeting ADC, or patients with carcinoma of
the salivary glands that have progressed after one line of systemic therapy
3. Documented history of erbb2 amplification.
4. Patients must have received at least one line of an approved or established therapy.
5. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Gastric Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 positive.
4. Patients must have received a first line of therapy that included a platinum salt and
a fluoropyridine in combination with trastuzumab or a biosimilar to trastuzumab.
5. Patients must have progressed after the first line therapy.
6. Patients must have received only one line of therapy for the treatment of metastatic
disease.
7. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Gastric Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
4. Patients must have received a first line of therapy that included a platinum salt and
a fluoropyridine in combination with an anti PD-1
5. Patients must have progressed after the first line therapy.
6. Progression while under anti PD-(L)1 must have occurred within 6 months of patient
inclusion
7. Patients must have received only one line of therapy for the treatment of metastatic
disease.
8. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
9. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Esophageal Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 positive.
4. Patients must have received a first line of therapy that included a platinum salt and
a fluoropyridine in combination with trastuzumab or a biosimilar to trastuzumab.
5. Patients must have progressed after the first line therapy.
6. Patients must have received only one line of therapy for the treatment of metastatic
disease.
7. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Esophageal Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
4. Patients must have received a first line of therapy that included a platinum salt and
a fluoropyridine in combination with an anti PD-1
5. Patients must have progressed after the first line therapy.
6. Progression while under anti PD-(L)1 must have occurred within 6 months of patient
inclusion
7. Patients must have received only one line of therapy for the treatment of metastatic
disease.
8. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
9. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have HER2 expression (at least 1+,
however, patients must not carry an erbb2 amplification) via archival or fresh biopsy
tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy OR must have recurrent or progressive disease within 6
months after completing platinum-based chemotherapy for local disease, including those
with actionable genetic alterations.
4. Patients must have received and progressed on or after anti-PD-(L)1 therapy including
those with actionable genomic alterations for which an approved treatment exists
5. Progression while under anti PD-(L)1 must have occurred within 6 months of patient
inclusion
6. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when
testing is available as per country/region standard of care practices); patients with
actionable mutations must have received and progressed on, have been intolerant to, or
not be a candidate for standard tyrosine kinase inhibitors (TKIs) (as available per
country/region standard of care practices).
7. A fresh tumor biopsy must be obtained during the screening window.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have amplification of erbb2 via archival
or fresh biopsy tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy OR must have recurrent or progressive disease within 6
months after completing platinum-based chemotherapy for local disease, including those
with actionable genetic alterations.
4. Patients must have received and progressed on or after anti-PD-(L)1 therapy including
those with actionable genomic alterations for which an approved treatment exists
5. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when
testing is available as per country/region standard of care practices); patients with
actionable mutations must have received and progressed on, have been intolerant to, or
not be a candidate for standard tyrosine kinase inhibitors (TKIs) (as available per
country/region standard of care practices).
6. Patients with an erbb2 amplification must provide archival tissue. If archival tissue
is not available, a fresh biopsy must be obtained during the screening window.
Exclusion Criteria:
1. Concurrent treatment with a non-permitted drug as in Non-Permitted Medicines and
Therapies section. Previous treatment with drugs that specifically target the HER2 pathway
(mAb or tyrosine kinase inhibitor [TKI]) is acceptable providing washout period (4 weeks
for mAbs or protein therapeutics and 2 weeks for a TKI).
2. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [with the
exception of palliative bone directed radiotherapy], immune therapy, or cytokine therapy
except for erythropoietin), major surgery (excluding prior diagnostic biopsy), concurrent
systemic therapy with steroids or other immunosuppressive agents, or use of any
investigational drug within 28 days before the start of study treatment. Short-term
administration of systemic steroids (i.e., for allergic reactions or the management of
immune-related adverse events [irAEs]) is allowed.
1. Note: Patients receiving bisphosphonates are eligible provided treatment was initiated
at least 14 days before the first dose of DF1001.
2. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin or cervical carcinoma in situ.
3. Rapidly progressive disease.
4. Active or history of central nervous system (CNS) metastases.
5. Receipt of any organ transplantation including autologous or allogeneic stem-cell
transplantation.
6. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window).
7. Preexisting autoimmune disease (except for patients with vitiligo) needing treatment
with systemic immunosuppressive agents for more than 28 days within the last 3 years
or clinically relevant immunodeficiencies (eg, dys-gammaglobulinemia or congenital
immunodeficiencies), or fever within 7 days of Day 1.
8. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 NCI-CTCAE v5.0), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly
controlled asthma).
9. Persisting toxicity related to prior therapy > Grade 1 NCI-CTCAE v5.0, however
alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
10. Pregnancy or lactation in females during the study.
11. Known alcohol or drug abuse.
12. Serious cardiac illness
13. NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)
14. High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate > 100/min at rest
15. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
Atrioventricular block (AV-block; second-degree AV-block Type 2 [Mobitz 2] or
third-degree AV-block)
16. Angina pectoris requiring anti-anginal medication
17. Clinically significant valvular heart disease
18. Evidence of transmural infarction on ECG
19. Poorly controlled hypertension (defined by: systolic > 180 mm Hg or diastolic > 100 mm
Hg)
20. Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary
disease or any clinically relevant medical condition in the opinion of the
Investigator that may limit participation in this study.
21. Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
22. All other significant diseases (e.g., inflammatory bowel disease), which, in the
opinion of the Investigator, might impair the patient's ability to participate
23. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
24. Legal incapacity or limited legal capacity.
25. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol .
Solid Tumor, Adult, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
A Phase 2 multi-center open-label basket trial of nab-sirolimus for adult and adolescent
patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or
TSC2 genes
Dustin Deming, MD
All
12 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05103358
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2
alteration. Genetic alterations should be identified using NGS in tumor tissue or
liquid biopsy).
• Patients will be enrolled after the central evaluation of NGS report confirms
eligibility.
2. Patients must have solid tumors that are metastatic or locally advanced where surgical
resection is not an option or likely to result in severe morbidity.
3. Patients must have received all standard therapies appropriate for their tumor type
and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the patient has no satisfactory alternative treatments.
4. Patients must have 1 or more measurable target lesions by computed tomography (CT)
scan or magnetic resonance imaging (MRI) (RECIST v1.1).
5. Age: 12 years or older.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky
Performance Status (KPS) ≥80 or Lansky play-performance scale for pediatric patients
≥80.
7. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver
metastases)
8. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault CCr =
((140-age) × weight[kg]) / (72 × SCr[mL/min]) × 0.85, if female
9. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be ≤350
mg/dL.
11. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of
prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a
single agent small-molecule therapeutic, and adequately recovered from the acute
toxicities of any prior therapy, including neuropathy, to Grade ≤1.
12. Male or non-pregnant and non-breastfeeding female:
1. Females of childbearing potential must agree to use effective contraception or
abstinence without interruption from 28 days prior to starting investigational
product (IP) throughout 3 months after last dose of IP and have a negative serum
pregnancy test (beta human chorionic gonadotropin, β-hCG) result at screening and
agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. A second form of birth control is required even if she
has had a tubal ligation.
2. Male patients must agree not to donate sperm and must practice abstinence or
agree to use a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study and throughout 3 months
after last dose of IP. A second form of birth control is required even if he has
undergone a successful vasectomy.
13. The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s)
the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.
Exclusion Criteria:
1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment.
3. Patients with primary brain tumors or PEComa.
4. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or
other conditions that could affect their participation including:
1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal
cord compression, untreated brain metastases or symptomatic or unstable brain
metastases. Note: Patients with stable brain metastases (defined as asymptomatic
or no requirement for high-dose [defined as dexamethasone 10 mg daily or higher]
or increasing dose of systemic corticosteroids) and without imminent need of
radiation therapy are eligible. If applicable, patients must have completed brain
radiation therapy and recovered adequately from any associated toxicity and/or
complications prior to eligibility assessment. For patients who have received
prior radiation therapy, post-treatment MRI scan should show no increase in brain
lesion size/volume.
2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart
Association, NYHA class III or IV), myocardial infarction ≤6 months prior to
first study treatment, serious uncontrolled cardiac arrhythmia or any other
clinically significant cardiac disease.
3. Pre-existing severely impaired lung function. If a patient has a pre-existing
pulmonary condition, eligible patients should have a spirometry and diffusing
capacity for carbon monoxide (DLCO) that is >50% of the normal predicted value
and/or O2 saturation that is >88% at rest on room air (Note: spirometry and
pulmonary function tests [PFTs] not required to be performed unless clinically
indicated).
4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy.
5. A history of malignancies other than the one under treatment unless the patient
is disease-free for more than 5 years from diagnosis. Note, controlled
non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental
prostate cancer, certain low grade hematologic malignancies (eg CLL, follicular
lymphoma, etc), or other adequately treated carcinoma-in-situ may be eligible,
after discussion with the medical monitor.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic
blood pressure ≥100 mm Hg).
7. Patients with history of interstitial lung disease and/or pneumonitis, or
pulmonary hypertension.
8. Individuals with known human immunodeficiency virus (HIV) infection are excluded
from this study as combination antiretroviral therapy could potentially result in
significant pharmacokinetic interactions. In addition, these individuals are at
increased risk of serious infections due to the immunosuppressive effects of mTOR
inhibition.
9. Active Hepatitis B or Hepatitis C, with detectable viral load.
5. Regarding concomitant medications with significant CYP3A4 and P-gp interactions,
discontinuation of strong inhibitors (eg, ketoconazole, itraconazole, voriconazole,
erythromycin, clarithromycin, telithromycin, and others), strong inducers (eg,
rifampin, rifabutin), and known CYP3A4 substrates with a narrow therapeutic window
(eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide,
quinidine, or terfenadine) is required at least 5 half lives prior to receiving the
first dose of nab-sirolimus, whichever is longer.
Tumor, Tumor, Solid, Metastasis, Metastatic Cancer, Cancer, Cancer Metastatic, Tumors, Neoplasms, Neoplasm Metastasis, Solid Tumor, Advanced Solid Tumor, Advanced Cancer, Malignant Solid Tumor, Malignant Solid Neoplasm, Malignant Neoplasm, Malignant Tumor, TSC, TSC1, TSC2, Metastatic Solid Tumor, Metastatic Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lung, Melanoma/Skin cancer, Sarcoma, Uterus
A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects (OPTIMUM)
The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination
with Vorinostat in patients with Recurrent or Progressive neuroblastoma
Kenneth Desantes, M.D.
All
1 Year and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03561259
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised
INRC criteria at the time of study enrollment with recurrent or progressive disease at
any time prior to enrollment, regardless of overall response to frontline therapy,
where frontline therapy includes a minimum of 4 cycles of induction therapy at any
time prior to enrollment.
2. May have had prior 131I-MIBG therapy, provided:
1. It has been at least 6 months from the date of last 131I-MIBG ;
2. Response was other than progressive disease on first restaging after 131I-MIBG ;
3. Prior 131I-MIBG was given as monotherapy and not in combination with systemic
anticancer agents;
4. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
3. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on
an (123I)-iobenguane scan, or
1. any progressive non-iobenguane avid lesion is proven by biopsy to be a
non-neuroblastoma lesion.
2. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by
routine imaging and confirmed by the investigator.
4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least
2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
5. If a male, must agree to use an adequate contraception method as deemed appropriate by
the Investigator (e.g., vasectomy, condoms) or partner using effective contraception
and to not donate sperm during the study and for 90 days after receiving the last dose
of study drug.
6. If a female of childbearing potential, have a negative serum pregnancy test result
prior to each dosing and, if sexually active, be practicing an effective method of
birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a
cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner
sterilization throughout the study.
7. Age at study entry ≥1 year.
8. Previous platelet transfusions are permitted, as long as the subject has a platelet
count ≥50,000/μL without transfusion support for at least 1 week.
9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
10. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
11. Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age,
and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate
aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of
normal (for all sites, the upper limit of normal for alanine aminotransferase is
defined as 45 U/L).
12. Normal thyroid function as measured by T4 or TSH or have abnormal results that are not
considered clinically important by the Investigator or may be receiving levothyroxine.
13. Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction
≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to
Visit 1 (Baseline).
14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance
Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
15. Full recovery from the toxic effects of any prior therapy.
16. Coagulation Function:
1. International Normalized Ratio (INR) < 1.5
2. Partial thromboplastin time (PTT) < 1.5 times upper limit of normal.
Exclusion Criteria:
1. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not
recovered from effects of any biologic therapy.
2. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
3. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit
1 are excluded. Those who have received allogeneic stem cell treatment more than 4
months from Visit 1 must have recovered and have no active graft versus host disease
(GVHD) to be eligible.
4. Subjects must not have received radiation for a minimum of 2 weeks prior to study
enrollment. Subjects whose only site(s) of disease have been radiated are eligible as
long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum
of 12 weeks prior to study enrollment is required following prior large field
radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space)
5. History of total body irradiation.
6. Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either
by creatinine clearance or radioisotope direct measurement or by calculation with the
Schwartz formula
7. Subjects who are on hemodialysis.
8. Pregnancy or breastfeeding.
9. Significant active infections including active hepatitis B, or hepatitis C infection,
or known infection with human immunodeficiency virus (HIV) (testing for HIV is not
required prior to study entry).
10. Clinically important cardiac, pulmonary, and hepatic impairment.
11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria
and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
1. Since valproic acid has HDAC inhibitory activity, patients must not have received
valproic acid within 30 days of study entry.
2. Since vorinostat may prolong the QT interval, patients must not be receiving
other medications known to prolong the QT interval at the time of study entry .
Pentamidine must not have been received within 1 week of study enrollment.
3. Patients with a history of deep venous thrombosis that was not associated with
the presence of a central venous catheter.
4. Patients who are receiving Coumadin.
Neuroblastoma, Neuroectodermal Tumors, Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
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