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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
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma, 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
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)
To assess:
- efficacy of APL-101 as monotherapy for the treatment of NSCLC harboring MET Exon 14
skipping mutations, NSCLC harboring MET amplification, solid tumors harboring MET
amplification, solid tumors harboring MET fusion, primary CNS tumors harboring MET
alterations, solid tumors harboring wild-type MET with overexpression of HGF and MET
- efficacy of APL-101 as an add-on therapy to EGFR inhibitor for the treatment of NSCLC
harboring EGFR activating mutations and developed acquired resistance with MET
amplification and disease progression after documented CR or PR with 1st line EGFR
inhibitors (EGFR-I)
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03175224
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Major
Inclusion Criteria:
1. Men and women 18 years of age or older.
2. 9 cohorts will be enrolled:
• Cohort A1 / Exon 14 NSCLC MET inhibitor naive in first line: Histologically or
cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies;
unresectable or metastatic disease (Stage 3b/4); treatment-naive subjects in
first line; not received any MET inhibitor and no known MET kinase inhibitor
resistance mutations
• Cohort A2 / Exon 14 NSCLC •MET inhibitor naïve: Histologically or cytologically
confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or
metastatic disease (Stage 3b/4); pretreated subjects refractory to or intolerant
of standard therapies with no more than three lines of prior therapy in the
unresectable or metastatic setting; not received any MET inhibitor and no known
MET kinase inhibitor resistance mutations
• Cohort B / Exon 14 NSCLC MET inhibitor experienced: ENROLLMENT COMPLETED
• Cohort C / MET amplification basket tumor types excluding primary CNS tumors: Any
solid tumor type regardless of histology excluding primary CNS tumors, with MET
amplification; unresectable or metastatic disease, refractory to or intolerant of
standard therapies, or refused standard therapies, or if therapy was unavailable
or unfeasible, with no more than 3 prior lines of therapy in the unresectable or
metastatic setting; not received any MET inhibitor and no known MET kinase
inhibitor resistance mutations
• Cohort C1 / MET amplification and wild-type EGFR NSCLC: NSCLC regardless of
histology, harboring MET amplification and wild-type EGFR; unresectable or
metastatic disease, previously untreated or treated with no more than 3 prior
lines of therapy in the unresectable or metastatic setting; not received any MET
inhibitor and no known MET kinase inhibitor resistance mutations
• Cohort C2 / EGFR positive NSCLC with acquired MET amplification (APL-101 Add-on
Therapy): Unresectable or metastatic NSCLC regardless of histology, harboring
EGFR activating mutations with acquired MET-Amplification as resistance mechanism
to the EGFR-I; developed resistance to first-line EGFR-inhibitor therapy after an
initial response (documented PR for at least 12 weeks); radiological
documentation of disease progression per RECIST on first-line EGFR inhibitor
therapy; currently on an EGFR-inhibitor therapy and agrees to receive APL-101 as
an add-on therapy during the study; no history of interstitial lung disease
(ILD)/pneumonitis, Grade ≥3 liver toxicity or QT prolongation with EGFR-I
therapy; not received any MET inhibitor and no known MET kinase inhibitor
resistance mutations
• Cohort D / MET fusion basket tumor types excluding primary CNS tumors: any solid
tumor type regardless of histology excluding primary CNS tumors; unresectable or
metastatic disease, refractory to or intolerant of standard therapies, or refused
standard therapies, or if therapy was unavailable or unfeasible, with no more
than 3 prior lines of therapy in the unresectable or metastatic setting; not
received any MET inhibitor and no known MET kinase inhibitor resistance mutations
• Cohort E / Primary CNS tumors with MET alterations: subjects with primary CNS
tumors who meet inclusion criteria of MET dysregulations defined as single or
co-occurred MET fusion including PTPRZ1-MET (ZM) fusion, MET Exon 14 skipping
mutations, or MET amplification; refractory to or intolerant of standard
therapies, or refused standard therapies, or if therapy was unavailable or
unfeasible, with no more than 3 prior lines of therapy in the unresectable or
metastatic setting; not received any MET inhibitor and no known MET kinase
inhibitor resistance mutations; neurological symptoms controlled on a
stable/decreasing dose of steroids for at least 2 weeks before C1D1
• Cohort F / Basket tumor types harboring wild-type MET with over-expression of HGF
and MET: any solid tumor type regardless of histology harboring wild-type MET
with overexpression of HGF and MET; Unresectable or metastatic disease,
refractory to or intolerant of standard therapies, or refused standard therapies,
or if therapy was unavailable or unfeasible, with no more than 3 prior lines of
therapy in the unresectable or metastatic setting; not received any MET inhibitor
and no known MET kinase inhibitor resistance mutations
3. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is
allowed.
4. Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target
lesion according to relevant criteria
5. ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score ≥70.
6. Acceptable organ function
7. For all prior anticancer treatment, a duration of 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.
8. Adequate cardiac function
9. Women of child-bearing potential must have a negative serum or Beta-hCG at screening
or evidence of surgical sterility or evidence of post-menopausal status
10. No planned major surgery within 4 weeks of first dose of APL-101
11. Expected survival (life expectancy) ≥ 3 months from C1D1
12. Provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe and
feasible) either from the primary or a metastatic site) or liquid biopsy sample (if
tumor tissue is insufficient or lacking, and approved by the sponsor) is required for
prospective central lab confirmation for study entry (subjects with previously
confirmed molecular status by the Sponsor designated central lab or FDA approved NGS
based MET testing may be exempted, subjected to Sponsor approval.
Major
Exclusion Criteria:
1. Hypersensitivity to APL-101, excipients of the drug product, or other components of
the study treatment regimen.
2. Known actionable mutation/gene rearrangement of EGFR (except for NSCLC subjects in
Cohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
3. Use or intended use of any other investigational product, including herbal
medications, through Study Treatment Termination.
4. Active uncontrolled systemic bacterial, viral, or fungal infection or clinically
significant, active disease process, which in the opinion of the investigator makes
the risk: benefit unfavorable for the participation of the trial.
5. Life-threatening illness, significant organ system dysfunction or comorbid conditions,
or other reasons that, in the investigator's opinion, could compromise the subject's
safety or the integrity of the study outcomes, or interfere with the absorption or
metabolism of APL-101.
6. 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, or concurrent treatment with a medication that is a known risk for
prolonging the QT interval. Chronic controlled atrial fibrillation is not excluded.
7. Historical seropositive results consistent with active infection for hepatitis C virus
(HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with
antiviral therapy and human immunodeficiency virus (HIV) positive subjects who are not
clinically stable or controlled on their medication (asymptomatic subjects with CD4+
T-cell (CD4+) counts ≥ 350 cells/μL and have not had an opportunistic infection within
the past 12 months prior to first dose of APL-101 would be eligible for study entry.
If history is unclear, relevant test(s) at Screening will be required to confirm
eligibility.
8. Known significant mental illness or other conditions such as active alcohol or other
substance abuse that, in the opinion of the investigator, predisposes the subject to
high risk of noncompliance with the protocol treatment or assessments.
9. Unable to swallow orally administered medication whole.
10. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption
11. Women who are breastfeeding
12. History of another malignancy within 3 years prior to C1D1. A subject with the
following malignancies is allowed if considered cured or unlikely to recur within 3
years:
1. Carcinoma of the skin without melanomatous features.
2. Curatively treated cervical carcinoma in situ.
3. Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in
situ (T1s), thyroid papillary cancer with prior treatment, prostate cancer which
has been surgically or medically treated and not likely to recur within 3 years.
13. Subjects who are unable or unwilling to discontinue excluded medications (drugs with
known QTc risk and known strong cytochrome P450 [CYP]3A4 inducer and/or strong
inhibitors) for at least 5 half-lives prior to first dose of study drug. Subjects may
qualify if such medication(s) can be safely replaced with alternate medications with
less risk of drug-drug interaction.
14. Subjects with active COVID-19 infection.
15. 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.
Solid Tumors, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme, EGFR Gene Mutation, MET Amplification, HGF, Thyroid Cancer, Pancreatic Cancer, Colon Cancer, MET Alteration, MET Fusion, Exon 14 Skipping, 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
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
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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
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
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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
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])
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, 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
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 one "1" (borderline), 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
• Neuroendocrine tumors including pheochromocytoma
• Melanocytic tumors, except clearly benign nevi
• Ganglioneuromas
• 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
Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neuroendocrine Neoplasm, Stromal 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, 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
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
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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
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
This phase III trial studies if selumetinib works just as well as the standard treatment with
carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to
see if selumetinib is better than CV in improving vision in subjects with LGG of the optic
pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that
low-grade glioma tumor cells need for their growth. This results in killing tumor cells.
Drugs used as chemotherapy, such as carboplatin and vincristine, 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. It is not yet known whether selumetinib works better in
treating patients with NF1-associated low-grade glioma compared to standard therapy with
carboplatin and vincristine.
Kenneth Desantes, M.D.
All
2 Years to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03871257
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Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or
germline genetic testing
• Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that
has not been treated with any modality other than surgery
• For patients with optic pathway gliomas (OPGs):
• Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms
(including visual dysfunction, as defined below) or other exam findings
associated with the tumor
• Previously-diagnosed patients with OPG are eligible if they have new or worsening
neurologic symptoms (including visual dysfunction, as defined below) or have
tumor growth
• For both newly-diagnosed and previously-diagnosed OPG, the patient may be
eligible, irrespective of whether there has been tumor growth or other
neurological symptoms or worsening, if they meet at least one of the following
visual criteria:
• Visual worsening, defined as worsening of visual acuity (VA) or visual
fields (VF) documented within the past year (by examination or history); OR
• Significant visual dysfunction (defined as VA worse than normal for age by
0.6 logMAR [20/80, 6/24, or 2.5/10] or more in one or both eyes)
• For patients with LGG in other locations (i.e., not OPGs):
• Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms
or other exam findings associated with the tumor
• NOTE: Newly-diagnosed patients with LGG without associated neurologic
symptoms or exam findings are not eligible
• Previously-diagnosed patients with LGG are eligible if they have new or worsening
neurologic symptoms or have tumor growth
• Although not required, if a biopsy/tumor resection is performed, eligible histologies
will include all tumors considered LGG or low-grade astrocytoma (World Health
Organization [WHO] grade I and II) by 5th edition WHO classification of central
nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients must have two-dimensional measurable tumor >= 1 cm^2
• Patients with metastatic disease or multiple independent primary LGGs are allowed on
study
• Creatinine clearance or radioisotope glomerular filtration Rate (GFR) >= 70
mL/min/1.73 m^2 OR a serum creatinine based on age/gender (within 7 days prior to
enrollment) as follows:
• Age; maximum serum creatinine (mg/dL)
• 2 to < 6 years; 0.8 (male) and 0.8 (female)
• 6 to < 10 years; 1 (male) and 1 (female)
• 10 to < 13 years; 1.2 (male) and 1.2 (female)
• 13 to < 16 years; 1.5 (male) and 1.4 (female)
• >= 16 years; 1.7 (male) and 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x
upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the
purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (within 4 weeks
prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should have not
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for
age, height, and gender at the time of enrollment. Patients >= 18 years of age must
have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the
use of antihypertensive medications).
• Note: Adequate blood pressure can be achieved using medication for the treatment
of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site(s) of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• For patients who undergo a surgery on the target tumor (not required), a pre- and
post-operative* MRI of the brain (with orbital cuts for optic pathway tumors) or spine
(depending on the site(s) of primary disease) with and without contrast must also be
performed within 4 weeks prior to enrollment
• The post-operative MRIs should be performed ideally within 48 hours after surgery
if possible
• 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 the ability to swallow whole capsules
• Patients must have receptive and expressive language skills in English or Spanish to
complete the quality of life (QOL) and neurocognitive assessments
• 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 must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior
surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/ condition, including
substance use disorders likely in the judgement of the investigator to interfere or
limit compliance with study requirements/treatment are not eligible
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• Cardiac conditions:
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Ophthalmologic conditions:
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Ophthalmological findings secondary to long-standing optic pathway glioma (such
as visual loss, optic nerve pallor, or strabismus) or longstanding
orbito-temporal plexiform neurofibroma (PN), such as visual loss, strabismus)
will NOT be considered a significant abnormality for the purposes of the study
• Treatments and/or medications patient is receiving that would make her/him ineligible,
such as:
• Supplementation with vitamin E greater than 100% of the daily recommended dose.
Any multivitamin containing vitamin E must be stopped prior to study enrollment
even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical
placement for vascular access or cerebrospinal fluid (CSF) diverting procedures
such as endoscopic third ventriculostomy (ETV) and ventriculo-peritoneal (VP)
shunt.
• Note: Patients must have healed from any prior surgery prior to enrollment
• Patients who have an uncontrolled infection are not eligible
Low Grade Glioma, Neurofibromatosis Type 1, Visual Pathway Glioma, Brain and Nervous System, Brain/Central Nervous System
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
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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
A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
The primary purpose of this study is to determine the antitumor activity of enfortumab
vedotin as measured by confirmed objective response rate (ORR) per RECIST v1.1.
This study will also assess other measures of antitumor activity; overall survival (OS); as
well as the safety and tolerability of enfortumab vedotin for cohorts 1 to 8 and enfortumab
vedotin + pembrolizumab in cohort 9.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04225117
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Inclusion Criteria:
• Subject is considered an adult according to local regulation at the time of signing
the informed consent form (ICF).
• Subject has measurable disease by RECIST Version 1.1.
• Subject has accessible archival tumor tissue from either the primary tumor or a
metastatic site, for which source and availability have been confirmed prior to study
treatment. If no archival tumor tissue is available, the subject will have a biopsy to
obtain tumor tissue prior to study treatment. If the subject is unable to undergo a
biopsy due to safety concerns, enrollment into the study must be discussed with the
medical monitor.
• For cohort 9 only: Subject should submit archival or fresh tumor tissue sample for
programmed cell death-ligand 1 (PD-L1) central testing during screening if no local
PD-L1 test result is available. Central test result for PD-L1 will be required prior
to subject enrollment. For cohort 9 subjects with local PD-L1 test result confirming
CPS ≥ 1, archival or fresh tissue sample for exploratory analysis should be submitted
within 5 days of enrollment.
• Subject has ECOG performance status of 0 or 1.
• Subject has the following baseline laboratory data. If a subject has received a recent
blood transfusion, the hematology tests must be obtained ≥ 28 days after any blood
transfusion.
• absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
• platelet count ≥ 100 × 10^9/L
• hemoglobin ≥ 9 g/dL
• serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for
subjects with Gilbert's disease
• creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards
or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can
also be used instead of CrCl).
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Subject agrees not to participate in another interventional study while receiving
study treatment in the present study.
• Additional contraceptive requirements exist for male and female subjects.
Disease Specific
Inclusion Criteria:
• Evidence of progression on or after the last regimen received.
• Locally advanced or metastatic disease that is not amenable to curative intent
treatment.
Cohort 1: HR+/HER2- breast cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor
[ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast
cancers and are not considered a candidate for further hormonal therapy. Subject will
be considered HR+ if biopsies show ≥ 1% expression of ER or PR as per current American
Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or
incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
count as a prior cytotoxic regimen if disease recurrence occurred during or
within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at
least 1 prior standard of care cytotoxic regimen in the incurable, unresectable
locally advanced or metastatic setting, and has not received > 2 prior lines of
cytotoxic therapy in the locally advanced or metastatic setting. No limit applies to
endocrine therapies. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a
line of cytotoxic therapy.
• Subject has progressed, relapsed, or discontinued for toxicity during or after
receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent
kinase (CDK) inhibitors. Prior therapy with CDK inhibitors is not required.
Cohort 2: triple negative breast cancer (TNBC)
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed TNBC; defined as unequivocal
TNBC histology (ER-negative/PR-negative/HER2-negative). This is defined by < 1%
expression of ER and PR by immunohistochemistry (IHC), and that are, for HER2, either
0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not
amplified) as per current ASCO/CAP guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or
incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
count as a prior cytotoxic regimen if disease recurrence occurred during or
within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at
least 1 prior standard of care cytotoxic regimen in the incurable, unresectable
locally advanced or metastatic setting, and has not received > 2 prior lines of
cytotoxic therapy in the locally advanced or metastatic setting. Poly(ADP-ribose)
polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
• Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1)
or an anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or
PD-L1 expression and local treatment guidelines and has progressed or discontinued
treatment due to toxicity, or therapy is contraindicated for subject.
Cohort 3: squamous non-small cell lung cancer (NSCLC)
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically or cytologically-confirmed squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any
component of neuroendocrine histology.
• Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma
kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations
are eligible if treated with mutation targeted therapy and have progressed,
relapsed, or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
1. Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months of completion.
2. Maintenance therapy does not constitute a new chemotherapy regimen provided there
was no progression after the initial platinum-based regimen.
3. Changing chemotherapy agents during platinum-based treatment for the management
of toxicities does not constitute a new chemotherapy regimen provided no
progression had occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 4: non-squamous non-small cell lung cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed non-squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any
component of neuroendocrine histology.
• Subjects with known EGFR, ALK, ROS, BRAF, or other actionable mutations are
eligible if treated with mutation targeted therapy and have progressed, relapsed,
or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
1. Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months of completion.
2. Maintenance therapy does not constitute a new chemotherapy regimen provided there
was no progression after the initial platinum-based regimen.
3. Changing chemotherapy agents during platinum-based treatment for the management
of toxicities does not constitute a new chemotherapy regimen provided no
progression has occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 5: second-line or later head and neck cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed head and neck cancer.
• Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors
and/or parotid gland tumors are not eligible for Cohort 5.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
• Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months after completion.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohorts 6, 7 and 8: gastric or gastroesophageal junction (GEJ) or esophageal adenocarcinoma
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed gastric, GEJ, or esophageal
cancer.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
• Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if
relapsed or progressed ≤ 6 months after completion.
• Subject must have received a HER2 directed therapy if known to have HER2 positive
cancer.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 9: 1L HNSCC
• Subject has histologically- or cytologically-confirmed head and neck squamous cell
carcinoma.
a. Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors and/or
parotid gland tumors are not eligible for Cohort 9.
• Subject has recurrent or metastatic disease that is incurable by local therapies.
• Subject's tumor sample has PD-L1 combined positive score (CPS) of ≥ 1 as determined by
local or central IHC testing.
• Subject has had no prior systemic therapy administered with the exception of systemic
therapy completed > 6 months prior if given as part of multimodal treatment for
locally advanced disease. Subjects who have received a PD-1 or PD-L1 inhibitor in the
curative setting are eligible if it has been at least 12 months since last dose of the
anti PD-L1 agent.
• Subject has ANC ≥ 1.5 × 10^9/L.
• International normalized ratio (INR) OR prothrombin time (PT) and activated partial
thromboplastin (aPTT) both ≤ 1.5 × ULN unless subject is receiving anticoagulant
therapy as long as PT or aPTT is within the therapeutic range of intended use of
anticoagulants. PTT may be used if local lab is unable to perform aPTT.
• For subjects with oropharynx tumors, subject has results from testing of HPV status by
p16 testing.
Exclusion Criteria:
For All Cohorts:
• Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
• Subject has active central nervous system (CNS) metastases. Subjects with treated CNS
metastases are permitted on study if all the following are true:
• CNS metastases have been clinically stable for ≥ 6 weeks prior to screening
• If requiring steroid treatment for CNS metastases, the subject is on a stable
dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks
• Baseline imaging scans show no evidence of new or enlarged brain metastasis
• Subject does not have leptomeningeal disease
• Subject has ongoing clinically significant toxicity (Grade 2 or higher with the
exception of alopecia) associated with prior treatment (including systemic therapy,
radiotherapy or surgery).
• Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or
panhypopituitarism are excluded. Subjects with ongoing immunotherapy-related colitis,
uveitis, myocarditis or pneumonitis, or subjects with other immunotherapy-related AEs
requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), are
excluded. Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or
panhypopituitarism may be enrolled when well maintained/controlled on a stable dose of
hormone replacement therapy (if indicated).
• Subject has a history of uncontrolled diabetes mellitus within 3 months before the
first dose of study treatment. Uncontrolled diabetes (within 3 months before first
dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with
associated diabetes symptoms (polyuria or polydipsia) that are not otherwise
explained. The lowest HbA1c during the screening period will be used to determine
eligibility.
• Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E
(MMAE) based antibody-drug conjugates (ADCs).
• Subject has a second malignancy diagnosed within 3 years before first dose of study
drug, or any evidence of residual disease from a previously diagnosed malignancy.
Subjects with non-melanoma skin cancer, localized prostate cancer treated with
curative intent with no evidence of progression, low-risk or very low-risk (per
standard guidelines) localized prostate cancer under active surveillance/watchful
waiting without intent to treat, or carcinoma in situ of any type (if complete
resection was performed) are allowed.
• Subject is currently receiving systemic antimicrobial treatment for viral, bacterial,
or fungal infection at the time of first dose of study treatment. Routine
antimicrobial prophylaxis is permitted.
• Subject has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg]
reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is
detected).
• Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or
2).
• Subject has documented history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction or cardiac symptoms
(including congestive heart failure) consistent with New York Heart Association Class
III-IV within 6 months prior to the first dose of study drug.
• Subject has major surgery within 4 weeks prior to first dose of study drug.
• Subject had radiotherapy, chemotherapy, biologics, investigational agents, and/or
antitumor treatment with immunotherapy that is not completed 2 weeks prior to first
dose of study drug.
• Subject has known hypersensitivity to enfortumab vedotin or to any excipient contained
in the drug formulation of enfortumab vedotin (including histidine, trehalose
dihydrate and polysorbate 20) OR subject has known hypersensitivity to
biopharmaceutical produced in Chinese hamster ovary cells.
• Subject has known active keratitis or corneal ulcerations. Subject with superficial
punctate keratitis is allowed if the disorder is being adequately treated.
• Subject has any condition which makes the subject unsuitable for study participation.
Cohort 9: 1L HNSCC
• Had PD within 6 months of completion of curatively intended systemic treatment for
locoregionally advanced HNSCC.
• Has had an allogeneic tissue/solid organ transplant. Has severe hypersensitivity
(≥grade 3) to pembrolizumab and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that
required steroids or has current pneumonitis / interstitial lung disease.
• Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan.
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease
(e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating
investigator.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
1. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment and is allowed.
2. Brief (<7 days) use of systemic corticosteroids is allowed when use is considered
standard of care.
3. Subjects with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or
resolved childhood asthma/atopy will not be excluded.
4. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or
local steroid injections will not be excluded.
5. Subjects with hypothyroidism that is stable with hormone replacement or Sjögren's
syndrome will not be excluded.
• Has an active infection requiring systemic therapy.
• Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent in the
recurrent/metastatic setting. If anti-PD-1 or anti-PD-L1 agent was given as part of
curative intent therapy, it must be at least 1 year since last dose.
• Has received a live vaccine within 30 days of planned start of study therapy. Examples
of live vaccines include, but are not limited to, the following: measles, mumps,
rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette
Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally
killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,
FluMist®) are live attenuated vaccines and are not allowed.
• Subject has active tuberculosis
Locally Advanced or Metastatic Malignant Solid Tumors, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Larynx, Lung, Breast, Eye and Orbit, Head and Neck, Melanoma/Skin cancer
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
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/Phase 2
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), (except in certain scenarios).
• 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
any or all of the drugs other than LY3537982 may be initiated within 21 days prior to
enrollment. Start of study treatment may be delayed to allow sufficient time for
recovery from treatment-related toxicity.
• For one part of the study, participants must have received at least one prior
oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
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 their disease is asymptomatic, radiographically stable for at least 30 days,
and they do not require treatment with steroids in the two-week period prior to study
treatment. 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.
• 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 Neoplasms, 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
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, 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
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 6 parts (Parts A, B, and E: monotherapy, Parts C and D:
combination therapy, and Part F for both monotherapy and 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
treatments known to confer clinical benefit or whose disease is indicated for
anti- programmed cell death protein 1 or programmed cell death ligand 1 (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.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatments known to confer clinical benefit; or, for participants who
will undergo combination therapy, have disease which is indicated for
anti-PD-(L)1 mAb monotherapy.
• 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, E, and F.
• 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, E and F: Must provide pre-treatment adequate tumor tissue sample
prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment
and on-treatment biopsies 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). 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 HER2 activated non-small
cell lung cancer, hormone receptor (HR) positive HER2 negative metastatic breast cancer, or
HER2 positive metastatic breast cancer. DF1001-001 will be administered as monotherapy or in
combination; combinations are DF1001 + nivolumab, DF1001 + Nab paclitaxel, and DF1001 +
sacituzumab govitecan-hziy.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04143711
Show full eligibility criteria
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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:
NSCLC (HER2 Activated) Exploratory Efficacy Cohorts •Monotherapy and
Combination with Sacituzumab Govitecan-hziy.
1. Have progression of unresectable locally advanced or metastatic NSCLC after last
systemic therapy (as confirmed by investigator) or be intolerant of last systemic
therapy.
2. Have HER2 overexpression status (IHC 2+ or 3+), or ERBB2 amplification, or HER2
activating mutation
3. Have recurrent or progressive disease during or after platinum doublet-based
chemotherapy.
4. Have received and progressed on or after anti-PD-(L)1 therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HR+/HER2-) Exploratory Efficacy Cohort -
Monotherapy and Combination with Sacituzumab Govitecan-hziy.
1. Documented evidence of HR+ metastatic breast cancer
2. Documented evidence of HER2- status.
3. Disease progression or recurrence after prior therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HER2+) Exploratory Efficacy Cohorts -
Combination with Sacituzumab Govitecan-hziy
1. Have histologically confirmed HER2+ breast cancer.
2. Have received prior treatment with trastuzumab, pertuzumab, ado-trastuzumab emtansine
(T-DM1), or trastuzumab deruxtecan (T-DXd).
3. Have progression of unresectable locally advanced metastatic breast cancer after last
systemic therapy or be intolerant of last systemic therapy.
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.
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 ebb2 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, or have no
standard therapy available, or standard therapy has failed.
2. 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 received a platinum containing chemotherapy and an anti PD-1 or
anti PD-L1 for the treatment of urothelial bladder cancer.
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+.
4. Patient must have progressed after one line of systemic chemotherapy.
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.
Inclusion Criteria:
Basket erbb2 amplified Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Documented history of erbb2 amplification.
3. Patients must have received at least one line of an approved or established therapy.
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.
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.
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.
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.
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.
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.
Exclusion Criteria:
1. 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 or 5 half-lives before the start of study
treatment. 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
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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
Clarifying the Optimal Application of SLT Therapy Trial (COAST)
The goal of this study is to understand if SLT performed at low energy is as effective as SLT
performed at standard energy, and also to see if repeating SLT at low energy once a year will
prevent or delay the need for daily eye drop medications better than waiting for SLT to wear
off before repeating it.
Yao Liu
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04967989
Show full eligibility criteria
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Inclusion Criteria:
1. Age 18 or older and in good health
2. Each eye with one of the following qualifying diagnoses (diagnoses may differ between
eyes):
1. High-risk ocular hypertension (OHT): IOP > 21 mmHg without glaucomatous optic
neuropathy (excavation, diffuse or focal thinning or notching of the neuroretinal
rim, visible nerve fiber layer defects, or asymmetry of the vertical cup-to-disc
ratio of >0.2 between eyes) [enrollment of trial participants with High-risk OHT
will be capped at 25% of total enrollment]
2. Mild primary open-angle glaucoma: glaucomatous optic neuropathy, visual field
mean deviation better than -6.0 dB with no points in the central 5° <15 dB (see
figure on next page)
3. Moderate primary open-angle glaucoma: glaucomatous optic neuropathy, visual field
mean deviation equal to or worse than -6.0 dB but no worse than -12.0 dB and no
central 5° points <15 dB or mean deviation -12.0 dB or better with 1 central 5°
points <15 dB (see figure on next page).
3. Each eye with BCVA 20/200 (UK 6/60) or better
Exclusion Criteria:
1. Use of topical IOP-lowering medications for more than 6 cumulative months at any time
in the past 5 years
2. Any history of IOP-lowering laser (prophylactic iridotomy not included) or surgical
procedure
3. Advanced POAG in either eye (worse than moderate POAG as defined above)
4. Glaucoma other than POAG (including pigmentary and pseudoexfoliation glaucoma) in
either eye
5. Mean IOP > 35 mmHg at either the screening or baseline visit in either eye
6. Narrow or closed angle (Shaffer Grade 0, 1, or 2) in either eye
7. Contraindications to SLT or any other study intervention
8. Any corneal pathology that would preclude accurate assessment of IOP by Goldmann
tonometry in either eye
9. Any intraocular surgical procedure within the past 6 months in either eye
10. Inability to attend all scheduled study visits
11. Pregnant or planning to become pregnant in the next 4 years
Glaucoma and Ocular Hypertension, Glaucoma, Other, Eye & Vision
Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis
Izokibep is a small protein molecule that acts as a selective, potent inhibitor of
interleukin-17A, to which it binds with high affinity. This study investigates izokibep in
subjects with active non-infectious, intermediate-, posterior- or pan-uveitis requiring
high-dose steroids.
Laura Kopplin
All
18 Years to 75 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT05384249
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Inclusion Criteria:
General
• Subject has provided signed informed consent including consenting to comply with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.
• 18 years to 75 years of age
Type of Subject and Disease Characteristics
• Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis
• Active disease defined by the presence of at least 1 of the following criteria in at
least 1 eye despite treatment with stable doses of corticosteroids for at least 2
weeks prior to day 1:
• Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
by dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography
(FA), and Spectral-Domain Optical Coherence Tomography (SD-OCT) to determine
whether a lesion is active or inactive (the central reading center assessment
using FA, fundus photography and/or SD-OCT is required to confirm eligibility
prior to day 1).
• ≥ 2+ vitreous haze (National Eye Institute [NEI]/Standardization of Uveitis
Nomenclature [SUN] criteria) by digital indirect ophthalmoscope and fundus
photography (the central reading center assessment using fundus photography is
required to confirm eligibility prior to day 1).
• Currently receiving treatment with oral corticosteroids (≥ 7.5 mg/day to ≤ 40 mg/day
oral prednisone/prednisolone or corticosteroid equivalent) at a stable dose for at
least 2 weeks prior to day 1.
Exclusion Criteria:
Disease-related Medical Conditions
• Subject with isolated anterior uveitis
• Subject with serpiginous choroidopathy
• Subject with confirmed or suspected infectious uveitis
• Subject with corneal or lens opacity that precludes visualization of the fundus or
that likely requires cataract surgery during the duration of the study
• Subject with intraocular pressure of ≥ 25 mmHg while on ≥ 2 glaucoma medications or
evidence of glaucomatous optic nerve injury
• Subject with severe vitreous haze that precludes visualization of the fundus prior to
first dose of study drug
• Subject has a contraindication for mydriatic eye drops OR subject cannot be dilated
sufficiently well to permit good fundus visualization
• Subject with best corrected visual acuity (BCVA) < 20 letters (Early Treatment
Diabetic Retinopathy Study [ETDRS]) in at least 1 eye prior to first dose of study
drug
• Subject with proliferative or severe non-proliferative retinopathy or clinically
significant macular edema due to diabetic retinopathy
• Subject with neovascular/wet age-related macular degeneration
• Subject with an abnormality of the vitreo-retinal interface with the potential for
macular structural damage independent of the inflammatory process
• Subject with a history of active scleritis ≤ 12 months of first dose of study drug
Other protocol defined Inclusion/Exclusion criteria may apply
Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack)
Retinitis pigmentosa (RP) is an inherited retinal degeneration caused by one of several
mistakes in the genetic code. Such mistakes are called mutations. The mutations cause
degeneration of rod photoreceptors which are responsible for vision in dim illumination
resulting in night blindness. After rod photoreceptors are eliminated, gradual degeneration
of cone photoreceptors occurs resulting in gradual constriction of side vision that
eventually causes tunnel vision. Oxidative stress contributes to cone degeneration.
N-acetylcysteine (NAC) reduces oxidative stress and in animal models of RP it slowed cone
degeneration. In a phase I clinical trial in patients with RP, NAC taken by month for 6
months caused some small improvements in two different vision tests suggesting that long-term
administration of NAC might slow cone degeneration in RP. NAC Attack is a clinical trial
being conducted at many institutions in the US, Canada, Mexico, and Europe designed to
determine if taking NAC for several years provides benefit in patients with RP.
Kimberly Stepien, MD
All
18 Years to 65 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05537220
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Inclusion Criteria:
General
• Ability and willingness to provide informed consent
• Age ≥ 18 and ≤65 years at time of signing Informed Consent Form
• Ability and willingness to comply with the study protocol and to participate in all
study visits and assessments in the investigator's judgement
• For candidates of childbearing potential: willingness to use a method of contraception
• Agreement not to take supplements other than vitamin A
Ocular Inclusion Criteria
• Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual
constriction of visual fields, and maintenance of visual acuity;
• In addition, an eye must meet the following criteria to be included in the study:
• Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 µm
and ≥1500 µm and with well-defined truncation at both the nasal and temporal sides;
• BCVA ≥ ETDRS letter score of 61 (20/60 Snellen equivalent);
• Sufficiently clear ocular media and adequate pupillary dilation to allow good quality
images sufficient for analysis and grading by central reading center.
Exclusion Criteria:
General Exclusion Criteria
• Active cancer within the past 12 months, except for appropriately treated carcinoma in
situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score
≤ 6 and stable prostate specific antigen for > 12 months
• Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or
anticipated to require hemodialysis or peritoneal dialysis during the study
• Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease
(COPD), history of thrombocytopenia not due to a reversible cause or other blood
dyscrasia
• Uncontrolled blood pressure (defined as systolic > 180 and/or diastolic > 100 mmHg
while at rest) at screening. If a patient's initial measurement exceeds these values,
a second reading may be taken 30 or more minutes later. If the patient's blood
pressure must be controlled by antihypertensive medication, the patient may become
eligible if medication is taken continuously for at least 30 days.
• History of other disease, physical examination finding, or clinical laboratory finding
giving reasonable suspicion that oral NAC may be contraindicated or that follow up may
be jeopardized
• Cerebrovascular accident or myocardial infarction within 6 months of screening
• Participation in an investigational study that involves treatment with any drug or
device within 6 months of screening
• Three relatives already enrolled in study
• Pregnant, breast feeding, or intending to become pregnant during the study treatment
period. Women of childbearing potential who have not had tubal ligation must have a
urine pregnancy test at screening.
• Known history of allergy to NAC
• Having taken NAC in any form in the past 4 months
• Phenylketonuria
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• Abnormal laboratory value including the value of alanine aminotransferase (ALT),
aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper
limit of normal
• Any major abnormal findings on blood chemistry, hematology, and renal function lab
tests that in the opinion of the Site Investigator and/or the Study Chair makes the
candidate not suitable to participate in the trial
• HIV or hepatitis B infection
Ocular Exclusion Criteria
• Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy
or pigmentary changes in the central macula
• Cystoid spaces involving the fovea substantially reducing vision
• Glaucoma or other optic nerve disease causing visual field loss or reduced visual
acuity
• Intra ocular pressure >27 mm Hg from two measurements. If a patient's initial
measurement exceeds 27 mm Hg, a second reading must be taken.
• Any retinal disease other than RP causing reduction in visual field or visual acuity
• Any prior macular laser photocoagulation
• Intraocular surgery within 3 months prior to screening
• High myopia with spherical equivalent refractive error > 8 diopters. If an eye has had
cataract surgery or refractive surgery, a pre-operative refractive error spherical
equivalent > 8 diopters is an exclusion
• Any concurrent ocular condition that might affect interpretation of results
• History of uveitis in either eye
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended
Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic
activity of RLY-2608, in advanced solid tumor patients with a
Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in
blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent
for patients with unresectable or metastatic solid tumors, RLY-2608 + fulvestrant and
RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) combination arms for
patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single
agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2
parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Kari Wisinski, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05216432
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Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local
assessment
•Other potentially oncogenic PIK3CA mutations may be considered but must be approved by
the Sponsor prior to enrollment.
Part 1 •Ability to provide archived tumor tissue or be willing to undergo pretreatment
tumor biopsy to assess PIK3CA status retrospectively Part 2 •Submit tumor tissue prior to
study drug initiation for determination of PIK3CA mutation retrospectively.
Key Inclusion for RLY-2608 Single Agent Arm
• [For Part 1]: Evaluable disease per RECIST v1.1
• [For Part 2]: Measurable disease per RECIST v1.1
• Disease that is refractory to standard therapy, intolerant to standard therapy, or has
declined standard therapy.
• Part 1- histologically or cytologically confirmed diagnosis of unresectable or
metastatic solid tumor
• Part 2 •Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the
following tumor types:
Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3:
cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head
and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid
tumors with PIK3CA double mutations
Key Inclusion for Combination Arms
• [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
• Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2-
unresectable or metastatic breast cancer that is not amenable to curative therapy.
Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or
perimenopausal females must have a histologically or cytologically confirmed diagnosis
of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative
therapy and must have been previously treated with GnRH agonist at least 4 weeks prior
to start of study drug
• [For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast
cancer with:
1. ≤1 line of chemotherapy,
2. ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and
3. ≥1 antiestrogen therapy including, but not limited to, selective
estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor
modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole,
anastrozole, exemestane), and
4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note:
Systemic local, loco-regional, or adjuvant treatment is not to be included in
enumeration or previous treatment
[For RLY-2608 + fulvestrant arm; Part 2, Group 2]: Received prior treatment with a PI3Kα
inhibitor and discontinued the inhibitor due to intolerance and not disease progression,
where intolerance is defined as treatment discontinuation due to treatment related AE (eg.
hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction
and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.
Key Exclusion Criteria
Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant arm,
Part 2, Group 2).
Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose
≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
History of hypersensitivity to PI3K inhibitors. For combination arms only: hypersensitivity
to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination.
For triple combination arms only: history of pneumonitis or interstitial lung disease.
For the single agent and combination arms other than with ribociclib: mean QT interval
corrected using Fridericia's formula (QTcF) >480 msec. For the combination arms with
ribociclib: mean QTcF ≥450 msec.
Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a
familial history of prolonged QT syndrome.
Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS
tumor that is associated with progressive neurologic symptoms
PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid 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, 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
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants (Uni-Rare)
This is an international, multicenter study with two components:
Registry
- A standardized genetic screening and a prospective, standardized, cross-sectional
clinical data collection
- Enrollment is open to all genes on the RD Rare Gene List
Natural History Study
- A prospective, standardized, longitudinal Natural History Study
- Enrollment opens gene-by-gene, based on funding and within-gene Registry enrollment The
study objectives are as follows.
Registry Objectives
1. Genotype Characterization
2. Cross-Sectional Phenotype Characterization (within gene)
3. Establish a Link to My Retina Tracker Registry (MRTR)
4. Ancillary Exploratory Studies - Pooling of Genes
Natural History Study Objectives
1. Natural History (within gene)
2. Structure-Function Relationship (within gene)
3. Risk Factors for Progression (within gene)
4. Ancillary Exploratory Studies - Pooling of Genes
Kimberly Stepien, MD
All
4 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05589714
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Inclusion Criteria:
Participants must meet all the following inclusion criteria at the
Registry/Screening Visit to be eligible to enroll into the genetic screening phase:
1. Willing to participate in the study and able to communicate consent during the consent
process
2. Willing and able to complete all applicable Registry/Screening Visit assessments
3. Age ≥ 4 years
4. Must have a single gene on the RD Rare Gene List which meets one of the Genetic
Screening Criteria below based on a genetic report* from a clinically certified lab
(or from a research lab which has been approved by the study Genetics Committee):
Inheritance Pattern is Recessive and has at least 2 disease-causing variants which are
homozygous or heterozygous in trans
OR
Inheritance Pattern is Recessive and has 2 disease-causing variants with unknown phase and
meets all the following additional informatic criteria that is consistent with likely
segregation in trans:
1. Investigator confirms genotype and phenotype are consistent with autosomal recessive
inheritance
2. The 2 disease-causing variants have not been reported in cis in variant databases
3. No additional potentially pathogenic variants were found on the gene (and the
sequencing data for the gene were sufficiently robust to detect any additional
potentially pathogenic variants)
4. No potentially pathogenic variants were found in other common, likely candidate genes
for the proposed condition
OR
Inheritance Pattern is Dominant, X-linked, or Mitochondrial and has at least 1
disease-causing variant
Both eyes must meet the following criteria at the Registry/Screening Visit to enroll into
the genetic screening phase:
1. Both eyes must have a clinical diagnosis of retinal dystrophy
2. Both eyes must permit good quality photographic imaging (e.g., but not limited to,
clear ocular media, adequate pupil dilation, stable fixation)
Exclusion Criteria:
Participants must not meet any of the following exclusion criteria at the
Registry/Screening Visit to be eligible to enroll into the genetic screening phase:
1. History of more than 1 year of cumulative treatment, at any time, with an agent
associated with pigmentary retinopathy including amiodarone, chloroquine, deferoxamine,
hydroxychloroquine, pentosan polysulfate, tamoxifen, and deferoxamine Note: Since this is
an observational study, pregnant women will not be specifically excluded from
participation. However, minors that are pregnant shall be precluded from participation
until they become the age of majority.
Ocular
Exclusion Criteria:
If either eye has any of the following ocular exclusion criteria at the Registry/Screening
Visit, then the participant is not eligible to enroll into the genetic screening phase:
1. Current vitreous hemorrhage
2. Current complications of pathological myopia (for example, but not limited to, myopic
maculopathy including atrophy, scar, choroidal neovascularization, schisis) that could
inhibit ability to obtain good quality photographic imaging
3. History of intraocular surgery (for example, but not limited to, cataract surgery,
vitrectomy, penetrating keratoplasty, or LASIK) within 3 months of Registry/Screening
Visit
4. Current or any history of confirmed diagnosis of glaucoma (for example, but not
limited to, glaucomatous VF changes or nerve changes, or history of glaucoma filtering
surgery)
5. Current or any history of retinal vascular occlusion or proliferative diabetic
retinopathy
6. History or current evidence of ocular disease that, in the opinion of the
Investigator, may confound assessment of visual function (for example, but not limited
to, tractional or rhegmatogenous retinal detachment, any vitreoretinal surgery,
retinal vascular occlusion, proliferative diabetic retinopathy)
7. The following medications and treatments are prohibited as they can affect progression
of retinitis pigmentosa (RP). The participant must not have received the following
treatments:
Any use of ocular stem cell or gene therapy Any treatment with ocriplasmin Treatment
with Ozurdex (dexamethasone), Iluvien, or Yutiq (fluocinolone acetonide) intravitreal
implant
8. The following medications and treatments are excluded within the specified timeframe:
Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date
is less than 9 months prior to Registry/Screening Visit date)
Treatment with any other product within five times the expected half-life of the product
(time from last treatment date to Registry/Screening Visit date is at least 5 times the
half-life of the given product)
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase
III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma
(VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine
and dactinomycin (VA) and examines the use of centralized molecular risk stratification in
the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients
with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with
VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment.
Finally, this study examines the effect of therapy intensification in patients who have RMS
cancer with DNA mutations to see if their outcomes can be improved.
Kenneth Desantes, M.D.
All
up to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05304585
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Inclusion Criteria:
• All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular
Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032
(this trial).
• Patients must be =< 21 years at the time of enrollment.
• Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle
cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS)
(institutional FOXO1 fusion results are acceptable). RMS types included under 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). Enrollment
in APEC14B1 is required for all patients.
• All patients will be evaluated for stage and clinical group. Note that clinical
group designation assigned at the time of enrollment on study remains unchanged
regardless of any second-look operation that may be performed.
• Patients will be eligible for the very low-risk stratum (Regimen VA) if they
have Stage 1, CG I disease.
• Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they
have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III
(orbit only) disease.
• Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling
(SIRLNS) is required for all patients >= 10 years of age with paratesticular
tumors who do not have gross nodal involvement on imaging.
• Extremity Tumors: Regional lymph node sampling is required for histologic
evaluation in patients with extremity tumors.
• Clinically or radiographically enlarged nodes must be sampled for histologic
evaluation.
• Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for
patients > 16 years of age) performance status score of >= 50. 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 performance score.
• Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to
enrollment).
• Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on
age/gender as follows:
• Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4
(female)
• Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5
(female)
• Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
• Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2
(female)
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4
(female)
• Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• If there is evidence of biliary obstruction by the tumor, then the total
bilirubin must be < 3 x ULN for age.
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L.
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L (within 7 days prior to enrollment).
• 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 who have received prior chemotherapy and/or radiation therapy for cancer
prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
• Patients who have received 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 is sensitive substrate of the 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.
• Patients unable to undergo radiation therapy, if necessary, as specified in the
protocol.
• Evidence of uncontrolled infection.
• 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.
Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, 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
MC1R-targeted Alpha-particle Therapy Trial in Adults With Advanced Melanoma
In this first-in human, phase I/IIa study, the safety and efficacy of [212Pb]VMT01, an
alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R)
is being evaluated in patients with unresectable and metastatic melanoma.
Zachary Morris, MD
All
18 Years to 90 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05655312
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Inclusion Criteria:
• Ability to understand and willingness to provide informed consent, willingness to
comply with all study procedures for the duration of the study
• Male or female, aged ≥ 18 years
• Diagnosed with Stage IV metastatic melanoma, or unresectable Stage III
• Previously progressed (clinical or radiological progression) on at least one prior
therapy for metastatic melanoma
• Uptake of [68Ga]VMT02 or [203Pb]VMT01 by PET or SPECT imaging observed in at least one
melanoma tumor site using quantitative imaging analysis compared to reference normal
tissue
• Subjects on prior intravenous therapy (e.g., chemotherapy or checkpoint inhibitors),
or prior oral therapy (e.g., BRAF or MEK inhibitors) who demonstrate MC1R positivity
during screening are eligible for enrollment, provided that they undergo a wash-out
period of 21 days, or 14 days, respectively, prior to Day 1 treatment with
[212Pb]VMT01.
• Presence of measurable disease by RECIST v1.1 criteria assessed within 30 days prior
to the start of Day 1
• Ability to lie flat and still for up to two hours for imaging scans; moderate
conscious sedation allowed if indicated
• For females of reproductive potential: use of highly effective contraception for at
least one month prior to screening, and agreement to use such a method during study
participation and for an additional four weeks after the last administration of an
investigational product
• For males of reproductive potential: use of condoms or other methods to ensure
effective contraception with partner during study participation and for an additional
four weeks after the last administration of an investigational product
• ECOG performance score of < 2 at Screening
• Life expectancy of at least 3 months
• Evidence of sufficient organ function as determined by all of the following:
Oxygen saturation > 90% on room air eGFR > 50 mL/min/1.73m2 by CKD-EPI equation Complete
blood count with differential, within 7 calendar days prior to therapy and off Growth
Factors White blood cells (WBC) > 2500/mm3 Hemoglobin (Hgb) > 9.0 g/dL Platelets >
60,000/mm3 Absolute Neutrophil Count (ANC) > 1,250/mm3
The comprehensive metabolic panel, within seven calendar days prior to Day 1, demonstrating
values within the site's upper limit of normal (ULN), with the following exceptions:
Alanine aminotransferase (ALT) < 3x ULN Aspartate aminotransferase (AST) < 3x ULN Alkaline
phosphatase (ALP) < 2.5x ULN
Exclusion Criteria:
• Active secondary malignancy
• Prior treatment (for any reason) with radioactive nuclides; however, imaging tracers
are acceptable
• Pregnancy or breastfeeding a child
• Active infection
• Brain metastasis requiring acute therapy of any modality (i.e., surgical or external
beam radiotherapy) within two weeks of enrollment or clinical instability, including
signs or symptoms of brain edema. Subjects must demonstrate stable or decreasing brain
metastasis by a noninvasive imaging scan and must be off steroids or on decreasing
doses prior to enrollment.
• Treatment with another investigational drug product (therapeutic IND agents) within
the last 30 days.
• Current abuse of alcohol or illicit drugs
• Existence of any medical or social issues likely to interfere with study conductor
that may cause increased risk to the subject or to others, e.g., lack of ability to
follow radiation safety precautions
Melanoma, Skin, Melanoma/Skin cancer, Melanoma (Skin), Metastatic Melanoma, Melanoma Stage IV, Melanoma, Uveal, Mucosal Melanoma, Melanoma Stage III
An Observational Study of the Progression of Intermediate Age-Related Macular Degeneration (HONU)
This is a multicenter prospective study in participants with intermediate age-related macular
degeneration (iAMD). One primary objective of this study is to assess iAMD disease
progression, by the timeline and rates of conversion for high-risk iAMD at baseline to more
advanced atrophic AMD stages. The other primary objective of this observational study is to
assess the feasibility of measuring the rate of photoreceptor loss as a potential clinical
endpoint. The study will consist of an observation period of approximately 3 years (~144
weeks) for participants.
Mihai Mititelu, MD, MPH
All
50 Years to 94 Years old
N/A
This study is NOT accepting healthy volunteers
NCT05300724
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Inclusion Criteria:
• For women of childbearing potential, agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception, during the study for at least 28 days
after the last fluorescein injection for the fluorescein angiography (FA)
administration
• Study eye: High-risk intermediate AMD
Exclusion Criteria:
• Macular disease in either eye with subretinal deposits not typical of AMD
• Pigmentary abnormalities of the retina in either eye not typical of AMD
• Atrophy in either eye due to causes other than AMD
• Study eye: Any concurrent or history of ocular or intraocular condition
• Study eye: Intraocular surgery, including cataract surgery, within 3 months prior to
Day 1
• Study eye: Retinal tears or peripheral retinal breaks within 3 months prior to Day 1
• Study eye: Concurrent or history of retinal laser photocoagulation or anti-vascular
endothelial growth factor (anti-VEGF) treatment for exudative MNV, diabetic macular
edema, retinal vein occlusion, or proliferative diabetic retinopathy
• Study eye: Presence of choroidal nevus with overlying drusen in the circle with a
radius 3600 micrometer centered on the fovea
• Study eye: Previous participation in interventional clinical trials for GA or early
stages of AMD, except for vitamins and minerals, regardless of the route of
administration within the last 6 months, except for sham-arm participants
• Study eye: History of glaucoma surgery, corneal transplant, retinal pigment epithelium
tear, retinal tear that involves the macula, retinal detachment
• Either eye: Uncontrolled progressive glaucoma
• Either eye: Moderate or severe non-proliferative diabetic retinopathy or proliferative
diabetic retinopathy
• Either eye: History of recurrent infectious or inflammatory ocular disease
• Any concurrent or history of taking medications that can induce retinal toxicity
This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)
This study is open to adults with different types of advanced cancer (solid tumors). The
purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the
participants can tolerate. The most suitable dose is used in the second part to find out
whether brigimadlin makes tumors shrink.
In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called
MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet.
Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every
4 weeks.
The participants are in the study for as long as they benefit from and can tolerate
treatment. The doctors regularly check the participants' general health during the study.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03449381
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Inclusion Criteria:
• Provision of signed and dated, written informed consent form ICF in accordance with
ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or
analyses.
• Pathologically documented, advanced solid tumors.
• Patients fulfilling one or more of the following criteria:
• Radiologically documented disease progression or relapse
• Patients who are not eligible to receive standard of care treatments, and for
whom no proven treatments exist.
• Patients with MDM2 amplified sarcomas who require first line treatment (for Ph
Ib/dose expansion •Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria
to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status,
and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any
line of therapy. If TP53 status is not available during screening, the patient may be
included with unknown TP53 status if a tissue sample is submitted for central
laboratory assessment. If TP53 status cannot be evaluated, the patient may be included
if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract
(including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and
ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous
line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated
the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.
• Phase Ib (expansion phase) only:
• At least one target lesion that can be accurately measured per RECIST v.1.1.
• Phase Ia:
• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker,
and PGx analyses.
• Phase Ib:
• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses
and blood sampling for PK, pharmacodynamics, and biomarker analyses.
• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression
during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g.
inaccessible lesions or patient safety concern), an archived specimen, collected
before screening within 12 months of enrollment, may be submitted. If these
requirements cannot be met, then the patient may be allowed to enter the study at
Sponsor discretion, after agreement between the Investigator and Sponsor.
• Further inclusion criteria apply
Exclusion Criteria:
• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX
(MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated
brain metastases may participate provided they are stable, without evidence of
progression by imaging (using the identical imaging modality for each assessment,
either MRI or computed tomography (CT) scan), for at least four weeks prior to the
first dose of trial treatment, and any neurologic symptoms have returned to baseline;
have no evidence of new or enlarging brain metastases. Patients on corticosteroids
must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12
weeks prior to start of study treatment, or planned within 12 months after screening
(e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3
years prior to screening, except appropriately treated basal cell carcinoma of the
skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by
local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug
considered likely to interfere with the safe conduct of the trial.
• Further exclusion criteria apply.
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, 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
Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene
This phase I trial tests the safety, side effects, and best dose of neratinib in combination
with trastuzumab deruxtecan in treating patients with solid tumors that have spread to other
parts of the body (metastatic) or that cannot be removed by surgery (unresectable), and have
changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a
class of medications called kinase inhibitors. It works by blocking the action of an abnormal
protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor
cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates.
It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug,
called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and
delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to
shrink cancer with a change in the HER2 gene.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05372614
Show full eligibility criteria
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Inclusion Criteria:
• Patients must have histologically confirmed malignancy that is metastatic or
unresectable with participation in this clinical trial determined to be the best
option for next treatment in the opinion of the investigator
• Patients must have a solid tumor with HER2-positivity as determined by any one or more
of the following:
• HER2 overexpression defined by IHC 3+
• ERBB2 amplification by ISH or next-generation sequencing as determined by any
CLIA certified lab
• A known HER2 activating mutation
• HER2 overexpression by IHC/ISH will follow histology specific ASCO-CAP guidelines
for breast and gastric cancers. For tumor histologies without specific guidelines
the following criteria will apply:
• HER2 IHC should be performed first, followed by ISH methods in cases showing
2+ (equivocal) expression by IHC. Positive (IHC 3+) or negative (IHC 0 or
1+) do not require further ISH testing. Cases with HER2:CEP17 ratio ≥2 or an
average HER2 copy number ≥6.0 signals per cell are considered positive by
ISH
• Known HER2 activating mutations:
• G309A/E
• S310F/Y
• S653C
• V659E
• G660D
• R678Q
• E693K
• Q709L
• L755S/P
• Del. 755-759
• D769Y/H
• G776V/C
• V777L
• V842I
• T862A
• L869R
• H878Y
• All exon 20 insertions, including:
• A771_Y772insYVMA
• A775_G776insYVMA
• Y772_A775dup
• P780_Y781insGSP
• G778_P780dup
• V697L
• T733I
• D769N
• L841V
• L866M
• R896C
• If a different mutation is identified, contact the study chair for conferral.
Synonymous mutations are not eligible
• Patients must have received at least 1 prior line of therapy in the
advanced/metastatic setting. No limitation on number of prior therapies; however,
patients may not have received neratinib or DS-8201a previously. Prior HER2-targeted
therapy other than neratinib or DS-8201a is allowed (e.g., trastuzumab, pertuzumab,
TDM-1, lapatinib, etc.)
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of neratinib in combination with DS-8201a in patients < 18 years of age,
children are excluded from this study
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
(Karnofsky >= 70%)
• Hemoglobin >= 9.0 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 14 days of
enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior
to screening assessment
• Serum albumin >= 2.5 g/dL (within 14 days of enrollment)
• Leukocytes >= 3.0 K/cumm (within 14 days of enrollment)
• Absolute neutrophil count >= 1.5 K/cumm (within 14 days of enrollment)
• No administration of granulocyte colony-stimulating factor (G-CSF) is allowed
within 1 week prior to screening assessment
• Platelets >= 100 K/cumm (within 14 days of enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior
to screening assessment
• Total bilirubin =< 1.5 × institutional upper limit of normal (ULN), (< 3 × ULN in the
presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14
days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x ULN (if liver metastases are present =< 5 x ULN) (within 14 days of enrollment)
• International normalized ratio (INR)/prothrombin time (PT) and activated partial
thromboplastin time (aPTT) =< 1.5 x institutional ULN (within 14 days of enrollment)
• This applies only to patients who are not receiving therapeutic anticoagulation
that may affect INR. Those who are on therapeutic anticoagulation, should be on a
stable dose for 4 weeks and should be considered within therapeutic range
• Creatinine =< 1.5 x institutional ULN OR Glomerular filtration rate (GFR) >= 30
mL/min/1.73 m^2 (using the Cockcroft-Gault equation) (within 14 days of enrollment)
• Patients who are human immunodeficiency virus (HIV)-positive may participate IF they
meet the following eligibility requirements:
• They must be stable on their anti-retroviral regimen, and they must be healthy
from an HIV perspective
• They must have a CD4 count of greater than 250 cells/mcL over the past 6 months
on this same anti-retroviral regimen and must not have had a CD4 count < 200
cells/ul over the past 2 years, unless it was deemed related to THE CANCER AND/OR
CHEMOTHERAPY-induced bone marrow suppression
• For patients who have received chemotherapy in the past 6 months, a CD4
count < 250 cells/ul during chemotherapy is permitted as long as viral loads
were undetectable during this same chemotherapy
• They must have an undetectable viral load and a CD4 count >= 250 cells/uL within
7 days of enrollment
• They must not be currently receiving prophylactic therapy for an opportunistic
infection and must not have had an opportunistic infection within the past 6
months HIV-infected patients should be monitored every 12 weeks for viral load
and CD4 counts
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if the following criteria are met:
1) follow-up brain imaging done at least in 4 weeks after central nervous system
(CNS)-directed therapy shows no evidence of progression and 2) the patient no longer
requires steroids, or is on a stable steroid dose > 4 weeks
• Patients with radiographically new or progressive brain metastases (active brain
metastases) or leptomeningeal disease are eligible only if has no progressive clinical
symptoms and if the treating physician determines that immediate CNS specific
treatment is not required and is unlikely to be required during the first cycle of
therapy
• Patients should be New York Heart Association functional classification of class 2B or
better
• Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an
echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before
randomization/enrollment
• Dose expansion phase (PD cohort): Patients must have disease that is evaluable or
measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Dose expansion phase (PD cohort): Patients must have at least one lesion suitable for
biopsy without significant risk to the patient. The biopsiable lesion can be the same
as the evaluable lesion for response by RECIST 1.1
• Patients who had clinically significant side effects from prior cancer therapy must
have recovered to grade 1 or below
• HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as other
therapeutic agents used in this trial are known to be teratogenic; thus, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry, for the duration of
study participation, and for at least 1 month after the last dose of neratinib, or at
least 7 months after the last dose of DS-8201a, whichever is longer (women of
childbearing potential [WOCBP] only). Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 3 months after the last dose of neratinib, or 4 months after
completion of DS-8021a administration, whichever is longer
• Women of non-child-bearing potential defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous
follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L]
is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose
menopausal status is in doubt will be required to use one of the contraception methods
outlined for women of child-bearing potential if they wish to continue their HRT
during the study. Otherwise, they must discontinue HRT to allow confirmation of
post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4
weeks will elapse between the cessation of therapy and the blood draw; this interval
depends on the type and dosage of HRT. Following confirmation of their post-menopausal
status, they can resume use of HRT during the study without use of a contraceptive
method
• Male subjects must not freeze or donate sperm starting at screening and throughout the
study period, and at least 4 months after the final study drug administration.
Preservation of sperm should be considered prior to enrollment in this study
• Female subjects must not donate, or retrieve for their own use, ova from the time of
screening and throughout the study treatment period, and for at least 7 months after
the final study drug administration
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity who have a legally-authorized
representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
• With the exception of medications that are under investigation in the study (e.g.,
standard of care, comparators, or combination therapies), the following medications,
treatment, and procedures will be prohibited during the treatment period. The sponsor
must be notified if a subject receives any of these during the study:
• Other anticancer therapy, including small-molecule targeted agents within 2 weeks
or five half-lives, whichever is longer; chemotherapy otherwise not specified
(including, but not limited to cytotoxic chemotherapy, antibody drug conjugates,
retinoid therapy, hormonal therapy) within 3 weeks; immunotherapy or monoclonal
antibody within 4 weeks; and nitrosureas or mitomycin C within 6 weeks
(concurrent use of hormones for noncancer-related conditions [e.g., insulin for
diabetes and hormone replacement therapy] is acceptable)
• Other investigational therapeutic agents
• Patients who have had major surgery or radiation within 4 weeks; palliative
stereotactic radiation within 2 weeks (except for palliative radiation to known
metastatic sites as long as it does not affect assessment of response or
interrupt treatment for more than the maximum time specified in dose modification
section)
• Radiotherapy to the thorax (palliative radiation to known metastatic sites in the
thoracic spine is permitted in this study)
• Concomitant use of chronic systemic (IV or oral) corticosteroids or other
immunosuppressive medications except for managing adverse events (inhaled
steroids or intra-articular steroid injections are permitted in this study);
chronic replacement dose steroids (e.g., for those with adrenal insufficiency)
are permitted in this study
• Subjects with bronchopulmonary disorders who require intermittent use of
bronchodilators (such as albuterol) will not be excluded from this study
• Concomitant treatment with chloroquine or hydroxychloroquine is not allowed
during the study treatment due to concern for overlapping toxicities. If
treatment with chloroquine and hydroxychloroquine treatment is absolutely
required, study treatment must be interrupted. If chloroquine or
hydroxychloroquine is administered, then a wash-out period of more than 14 days
is required before restarting study treatment
• Patients with a history of (non-infectious) interstitial lung disease
(ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where
suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Patients with clinically severe pulmonary compromise resulting from intercurrent
pulmonary illnesses including, but not limited to, any underlying pulmonary disorder
(i.e. pulmonary emboli within three months of the study enrollment, severe asthma,
severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural
effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with
potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis,
etc.), or prior pneumonectomy
• Patients with history of allergic reactions attributed to compounds of similar
chemical or biologic composition to DS-8201a, the inactive ingredients in the drug
product, or neratinib
• Patients who have a history of severe hypersensitivity reactions to other monoclonal
antibodies
• Patients receiving any medications or substances that are moderate or strong
inhibitors or inducers of CYP3A4 and P-glycoprotein are ineligible. Avoid concomitant
use with proton pump inhibitors and P-glycoprotein substrates. Because the lists of
these agents are constantly changing, it is important to regularly consult a
frequently-updated medical reference. 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
• Patients with a medical history of myocardial infarction within 6 months before
enrollment, or symptomatic congestive heart failure (CHF) (New York Heart Association
class II to IV)
• Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or >
450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram
(ECG)
• Patients with clinically significant corneal disease in the opinion of the
investigator
• Patients with a pleural effusion, ascites, or pericardial effusion that requires
drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy
(CART). (Drainage and CART are not allowed within 2 weeks prior to screening
assessment) (GC indication)
• Patients with spinal cord compression
• Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or
antifungals
• Patients with unresolved toxicities from previous anticancer therapy, defined as
toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects
with chronic grade 2 toxicities may be eligible per the discretion of the investigator
after consultation with the sponsor medical monitor or designee (e.g., grade 2
chemotherapy-induced neuropathy)
• Patients with substance abuse or any other medical conditions such as clinically
significant cardiac or psychological conditions, that may, in the opinion of the
investigator, interfere with the subject's participation in the clinical study or
evaluation of the clinical study results
• Pregnant women are excluded from this study because DS-8201a is a HER2 antibody
conjugated to a topoisomerase 1 inhibitor 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 DS-8201a,
breastfeeding should be discontinued if the mother is treated with DS-8201a. These
potential risks may also apply to other agents used in this study
• Prior treatment with neratinib or DS-8201a
• Clinically significant chronic gastrointestinal disorder with diarrhea as a major
symptom; G2 or greater diarrhea at baseline. Please contact the study PI for any
patient with more than two episodes of diarrhea per day averaged over at least a 7 day
period at time of screening to determine whether the diarrhea would be considered
clinically significant
• Inability to swallow tablets
• Patients with active additional malignancy or a personal history of additional
malignancy that may affect outcome of disease under treatment (patients with a prior
or concurrent malignancy whose natural history or treatment does not have the
potential to interfere with the safety or efficacy assessment of the investigational
regimen at the discretion of the treating investigator are allowed)
• Patients with prior allogeneic organ transplantation including allogeneic stem cell
transplantation
Malignant Solid 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, 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
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
This study collects blood and tissue samples from patients with cancer and without cancer to
evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue
from patients with and without cancer to study in the laboratory may help researchers develop
tests for the early detection of cancers.
David Kosoff, MD
All
40 Years to 75 Years old
N/A
This study is also accepting healthy volunteers
NCT05334069
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Inclusion Criteria:
• Participants with a cancer diagnosis: Documentation of disease:
• Histologic documentation: Histologically confirmed diagnosis of invasive cancer
• Stage: Stage I-IV per American Joint Committee on Cancer (AJCC) 7th edition, with
the exception of patients with leukemia, lymphoma, and multiple myeloma
• For leukemia: Type (chronic lymphocytic leukemia [CLL], chronic myeloid
leukemia [CML], acute lymphoblastic lymphoma [ALL], acute myeloid leukemia
[AML])
• For lymphoma: Stage I-IV based on Ann Arbor staging
• For multiple myeloma: Stage I, II, III based on Revised International
Staging System (RISS)
• One of the following tumor types:
• Colorectal
• Bladder
• Head and neck
• Hepatobiliary
• Lung
• Lymphoma
• Leukemia
• Ovary *** For these specific cancer types only, patients may be enrolled
prior to histologic confirmation of malignancy. Sites are required to
contact the study chairs to review appropriateness for enrollment
• Pancreas *** For these specific cancer types only, patients may be enrolled
prior to histologic confirmation of malignancy. Sites are required to
contact the study chairs to review appropriateness for enrollment
• Multiple myeloma
• Gastric, esophageal or gastroesophageal
• Breast
• Thyroid
• Kidney
• For these specific cancer types only, patients may be enrolled prior to
histologic confirmation of malignancy. Sites are required to contact
the study chairs to review appropriateness for enrollment
• Endometrium
• Prostate
• Melanoma
*** For these specific cancer types only, patients may be enrolled prior to
histologic confirmation of malignancy. Sites are required to contact the
study chairs to review appropriateness for enrollment
• Sarcoma
• Participants with a cancer diagnosis: No prior definitive systemic or local
anti-cancer intervention
• Participants with a cancer diagnosis: Age >= 40 and =< 75
• Participants with a cancer diagnosis: No known current pregnancy by self-report
• Participants with a cancer diagnosis: No known or prior history of in situ or invasive
malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer
diagnosis
• Participants with a cancer diagnosis: Willingness to provide blood samples for
research use
• Participants with a cancer diagnosis: Absence of medical contraindications to a
research blood draw volume of 60 mL
• Participants with a cancer diagnosis: No history of organ transplantation
• Participants with a cancer diagnosis: Ability to read and comprehend English or
Spanish
* Eligibility is restricted to individuals who can comprehend and read English or
Spanish given that participation in the study will require the ability to read and
complete questionnaires that are available only in those two languages
• Participants without a cancer diagnosis and without suspicion of cancer: Age >= 40 and
=< 75
• Participants without a cancer diagnosis and without suspicion of cancer: No known
current pregnancy by self-report
• Participants without a cancer diagnosis and without suspicion of cancer: No known or
prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin
cancers)
• Participants without a cancer diagnosis and without suspicion of cancer: Willingness
to provide blood samples for research use
• Participants without a cancer diagnosis and without suspicion of cancer: Absence of
medical contraindications to a research blood draw volume of 60 mL
• Participants without a cancer diagnosis and without suspicion of cancer: No history of
organ transplantation
• Participants without a cancer diagnosis and without suspicion of cancer: Ability to
read and comprehend English or Spanish
* Eligibility is restricted to individuals who can comprehend and read English or
Spanish given that participation in the study will require the ability to read and
complete questionnaires that are available only in those two languages
• Participants with a high suspicion of cancer: High suspicion of ovarian cancer,
pancreatic cancer, kidney cancer, or melanoma by clinical and/or radiological
assessment, with plans for histologic or cytologic confirmation within 28 days after
study blood draw
* Examples of highly suspicious cases include: elevated CA125 and abnormal
transvaginal ultrasound, suspicious renal or pancreatic mass on imaging, suspicious
cutaneous lesion concerning for melanoma
• Participants with a high suspicion of cancer: Central review of radiology reports
and/or clinical documentation conducted by study chairs
• Participants with a high suspicion of cancer: Age >= 40 and =< 75
• Participants with a high suspicion of cancer: No known current pregnancy by
self-report
• Participants with a high suspicion of cancer: No known or prior history of in situ or
invasive malignancy (excluding in situ non-melanoma skin cancers) other than the
current cancer diagnosis
• Participants with a high suspicion of cancer: Willingness to provide blood samples for
research use
• Participants with a high suspicion of cancer: Absence of medical contraindications to
a research blood draw volume of 60 mL
• Participants with a high suspicion of cancer: No history or organ transplantation
• Participants with a high suspicion of cancer: Ability to read and comprehend English
or Spanish * Eligibility is restricted to individuals who can comprehend and read
English and Spanish given that participation in the study will require the ability to
read and complete questionnaires that are available only in those two languages
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, Uterus, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Ann Arbor Stage I Lymphoma, Ann Arbor Stage II Lymphoma, Ann Arbor Stage III Lymphoma, Ann Arbor Stage IV Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, Gastroesophageal Junction Adenocarcinoma, Head and Neck Carcinoma, Hematopoietic and Lymphoid Cell Neoplasm, Invasive Breast Carcinoma, Kidney Carcinoma, Malignant Hepatobiliary Neoplasm, Malignant Solid Neoplasm, Melanoma, Muscle-Invasive Bladder Carcinoma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, RISS Stage III Plasma Cell Myeloma, Sarcoma, Stage I Bladder Cancer AJCC v6 and v7, Stage I Breast Cancer AJCC v7, Stage I Colorectal Cancer AJCC v6 and v7, Stage I Esophageal Cancer AJCC V7, Stage I Gastric Cancer AJCC V7, Stage I Lung Cancer AJCC v7, Stage I Ovarian Cancer AJCC v6 and v7, Stage I Pancreatic Cancer AJCC v6 and v7, Stage I Prostate Cancer AJCC v7, Stage I Uterine Corpus Cancer AJCC v7, Stage II Bladder Cancer AJCC v6 and v7, Stage II Breast Cancer AJCC v6 and v7, Stage II Colorectal Cancer AJCC v7, Stage II Esophageal Cancer AJCC v7, Stage II Gastric Cancer AJCC v7, Stage II Lung Cancer AJCC v7, Stage II Ovarian Cancer AJCC v6 and v7, Stage II Pancreatic Cancer AJCC v6 and v7, Stage II Prostate Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7, Stage III Bladder Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Stage III Colorectal Cancer AJCC v7, Stage III Esophageal Cancer AJCC v7, Stage III Gastric Cancer AJCC v7, Stage III Lung Cancer AJCC v7, Stage III Ovarian Cancer AJCC v6 and v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage III Prostate Cancer AJCC v7, Stage III Uterine Corpus Cancer AJCC v7, Stage IV Bladder Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Colorectal Cancer AJCC v7, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7, Stage IV Lung Cancer AJCC v7, Stage IV Ovarian Cancer AJCC v6 and v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Stage IV Prostate Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7, Thyroid Gland Carcinoma
This is a pediatric basket study to investigate the safety and efficacy of afamitresgene
autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with
advanced cancers
Christian Capitini, MD
All
2 Years to 21 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05642455
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Inclusion Criteria:
• Age 2-21 years
• Body weight ≥ 10 kg
• Subject has histologically confirmed diagnosis of any one of the following cancers:
(A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
• Must have previously received a systemic chemotherapy
• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
• HLA-A*02 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Performance Status: ECOG 0-1 or Lansky Score ≥ 80
Exclusion Criteria:
• HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to fludarabine, cyclophosphamide.
• History of autoimmune or immune mediated disease
• Known central nervous system (CNS) metastases.
• Other prior malignancy that is not considered by the Investigator to be in complete
remission
• Clinically significant cardiovascular disease
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C
virus, or human T cell leukemia virus
• Pregnant or breastfeeding
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, 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, Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma
Study to Assess Batoclimab in Participants With Active Thyroid Eye Disease
To evaluate the efficacy of batoclimab 680 milligrams (mg) subcutaneous (SC) once a week (QW)
for 12 weeks followed by 340 mg SC QW for 12 weeks versus placebo on proptosis responder rate
at Week 24.
Suzanne Van Landingham
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05517421
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Inclusion criteria:
• Are ≥18 years of age at screening.
• Have a clinical diagnosis of TED associated with active, moderate to severe TED with
the following at screening and Visit 0:
• A CAS ≥ 4 in either eye, and
• Clinical evidence of worsened proptosis with:
1. Proptosis ≥ 18 mm and/or
2. Proptosis ≥ 3 mm increase from participant's baseline (prior to diagnosis of
TED), as estimated by the Investigator/assessor
• Have moderate to severe active TED, as defined by European Group on Graves'
Orbitopathy (EUGOGO) guidelines.
• Have onset of active TED within 12 months prior to screening.
• Have documented evidence of detectable anti-TSHR-Ab at screening.
• Are not expected to require immediate surgical intervention and are not planning
corrective surgery/irradiation or medical therapy for TED during the course of the
study.
• Are euthyroid with the baseline disease under control or have mild hypo- or
hyperthyroidism.
Additional inclusion criteria are defined in the protocol.
Exclusion criteria:
• Have decreased best corrected visual acuity due to optic neuropathy.
• Have at least a 2-point decrease in CAS or ≥2 mm decrease in proptosis between
screening and Baseline assessments in either eye.
• Have used any steroid (intravenous or oral) for the treatment of TED or other
conditions within 4 weeks prior to screening.
• Have used any steroid (Intravenous or oral) with a cumulative dose equivalent to ≥ 1 g
of methylprednisolone for the treatment of TED.
• Have known autoimmune disease other than TED, that, in the opinion of the
Investigator, would interfere with the course and conduct of the study.
• Had previous orbital irradiation or surgery for TED.
Additional exclusion criteria are defined in the protocol.
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