Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
PSMA-based 18F-DCFPyL PET/CT and PET/MRI Pilot Studies in Prostate Cancer
The overall goal of this research is to validate and develop a non-invasive imaging biomarker
of prostate cancer detection, progression, and recurrence. Development of such a biomarker
may be useful to differentiate indolent from aggressive prostate cancer phenotypes allowing
for selection of an appropriate risk adaptive therapy.
Steve Cho
Male
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT03232164
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Inclusion Criteria:
• Prostate cancer pathologically proven by prostate biopsy (newly diagnosed for
Sub-Study 1 and 4)
• Prostate biopsy histology grade ≥ Gleason 1, 6, 3+4, or 4+3; positive biopsy >2 cores
• Any PSA permitted
• Two consecutive rising PSA values (Sub-Study 3 only)
• Castrate-levels of testosterone •total testosterone < 50 ng/dL (Sub-Study 3 only)
• Patients considered as candidates for and medically fit to undergo prostatectomy
• At least 7 days after most recent prostate biopsy
• Imaging evidence of suspected metastatic disease, including CT, bone scan, MRI,
ultrasound or other PET modalities (Sub-Study 3 only)
• New diagnosis of prostate cancer undergoing additional biopsy evaluation (Sub--Study 4
only)
• Karnofsky performance status of at least 70 (Sub-Study 4 only)
• General health and anatomy suitable to undergo transrectal ultrasound-MRI fusion
biopsy of the identified lesions and standard 12 core sextent biopsy (Sub-Study 4
only)
Exclusion Criteria:
• Prior pelvic external beam radiation therapy or brachytherapy
• Chemotherapy for prostate cancer
• Androgen deprivation therapy for prostate cancer
• Investigational therapy for prostate cancer (Sub-Study 3 Only)
• Unable to lie flat during or tolerate PET/CT
• Prior history of any other malignancy within the last 2 years, other than skin basal
cell or cutaneous superficial squamous cell carcinoma that has not metastasized and
superficial bladder cancer.
• No prostatectomy scheduled more than 12 hours post imaging (Sub-Study 1 only)
• Serum creatinine > 2 time the upper limit of normal
• Total bilirubin > 3 times the upper limit of normal
• Liver Transaminases > 5 times the upper limit of normal
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
pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer
This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with
PD-1 blockade using pembrolizumab followed by treatment with pembrolizumab alone, and
delivered over a prolonged period of time (for a maximum of 2 years (32 cycles) or until
radiographic progression) on the treatment of castrate-resistant, metastatic prostate cancer.
The hypothesis to be tested is that delivering two vaccines with PD-1 blockade will elicit a
greater frequency and magnitude of tumor-directed CD8+ T cells, and thereby increase the
percentage of patients experiencing objective anti-tumor effect as measured by PSA declines
and/or objective radiographic responses. Participants must be 18 years of age or older and
can expect to be on treatment for 2 years (32 cycles) and on study for up to 4 years
(including 2 years of follow up via phone).
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04090528
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Inclusion Criteria:
• Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases
on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All participants must have received (and be receiving) standard of care androgen
deprivation treatment (surgical castration versus GnRH analogue or antagonist
treatment); subjects receiving Gonadotropin-releasing hormone (GnRH) analogue or
antagonist must continue this treatment throughout the time on this study.
• Participants may or may not have been treated previously with a nonsteroidal
antiandrogen. For participants previously treated with an antiandrogen, they must
be off use of anti-androgen for at least 4 weeks (for flutamide, apalutamide,
enzalutamide, or other 2nd generation AR antagonists) or 6 weeks (for
bicalutamide or nilutamide) prior to registration. Moreover, participants who
demonstrate an anti-androgen withdrawal response, defined as a > 25% decline in
PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible
until the PSA rises above the nadir observed after antiandrogen withdrawal.
• Participants must have a castrate serum level of testosterone (< 50 ng/dL) within
6 weeks of day 1
• Progressive disease while receiving androgen deprivation therapy defined by any one of
the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) bone
scan criteria or RECIST 1.1 during or after completing last therapy:
• PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week
intervals, with the final value > 2.0 ng/mL.
• Measurable disease: > 50% increase in the sum of the cross products of all
measurable lesions or the development of new measurable lesions. The short axis
of a target lymph node must be at least 15 mm by spiral CT to be considered a
target lesion
• Non-measurable (bone) disease: The appearance of two or more new areas of uptake
on bone scan (or Sodium Fluoride (NaF) positron emission tomography-computed
tomography (PET/CT)) consistent with metastatic disease compared to previous
imaging during castration therapy. The increased uptake of pre-existing lesions
on bone scan will not be taken to constitute progression, and ambiguous results
must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI).
• Prior treatment with abiraterone or enzalutamide is permitted, but participants must
have weaned to a daily corticosteroid dose equivalent of no more than 5 mg prednisone
daily for at least 28 days prior to day 1.
• Life expectancy of at least 6 months
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0, 1, or 2.
• Adequate hematologic, renal, liver, and coagulation function as evidenced by the
following within 6 weeks of day 1:
• White Blood Cells (WBC) >/= 2000 / mm3
• Absolute Neutrophil Count (ANC) >/= 1500 / mm3
• Hemoglobin (HgB) >/= 9.0 gm/dL (Participants must not have received a blood
transfusion within 14 days)
• Platelets >/= 100,000 / mm3
• Creatinine = 1.5 x institutional upper limit of normal (ULN)
• Total bilirubin = 1.5 x institutional ULN OR direct bilirubin = ULN for
participants with total bilirubin levels > 1.5 x ULN
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) = 2.5 x
institutional upper limit of normal
• Prothrombin Time (PT) or International Normalized Ratio (INR) = 1.5 x ULN
unless participant is receiving anticoagulant therapy and PT is within
therapeutic range of intended use of anticoagulant (only required for
participants receiving biopsy)
• Partial Thromboplastin Time (PTT) = 1.5 x ULN unless participant is receiving
anticoagulant therapy and a PTT is within therapeutic range of intended use of
anticoagulant (only required for participants receiving biopsy)
• No known history of human immunodeficiency viruses (HIV 1 and 2), Human T-cell
leukemia virus type 1 (HTLV-1), or active Hepatitis B or Hepatitis C
• Participants must be at least 4 weeks from any prior treatments and have recovered (to
< Grade 2) from acute toxicity attributed to this prior treatment, unless considered
chronic
• A subset of participants (6 participants per treatment arm) treated at the lead
University of Wisconsin (UW) site must be willing and able (in the opinion of the
treating physician) to undergo two research biopsies for the investigational component
of this trial.
• A subset of participants (6 participants per treatment arm) treated at the lead UW
site must be willing to undergo NaF PET/CT scans for the investigational component of
this trial.
• For those participants who are sexually active, they must be willing to use barrier
contraceptive methods, and refrain from donating sperm, during the period of treatment
on this trial and for four weeks after the last DNA immunization treatment
• Participants must be informed of the experimental nature of the study and its
potential risks, and must sign an Institutional Review Board (IRB)-approved written
informed consent form indicating such an understanding
Exclusion Criteria:
• Small cell or other variant (non-adenocarcinoma) prostate cancer histology, unless
there is evidence that the tumor expresses PAP
• Participants may not be receiving other investigational agents or be receiving
concurrent anticancer therapy other than standard androgen deprivation therapy
• Concurrent bisphosphonate therapy is not excluded, however participants should not
start bisphosphonate therapy while on this study; those participants already receiving
bisphosphonate therapy should continue at the same dosing and schedule as prior to
study entry
• Rapidly progressive symptomatic metastatic disease, as defined by the need for
increased opioid analgesics within one month of registration for the treatment of pain
attributed to a prostate cancer metastatic lesion; participants receiving opioids must
receive approval from the PI for eligibility
• Treatment with any of the following medications within 28 days of day 1, or while on
study, is prohibited:
• Systemic corticosteroids (at doses over the equivalent of 5 mg prednisone daily);
inhaled, intranasal or topical corticosteroids are acceptable
• Prostate Cancer and spes (PC-SPES)
• Megestrol
• Ketoconazole
• 5-α-reductase inhibitors •participants already taking 5-α-reductase inhibitors
prior to 28 days prior to registration may stay on these agents throughout the
course of therapy, but these should not be started while participants are on
study
• Diethyl stilbesterol
• Abiraterone
• Enzalutamide
• Apalutamide
• Radium 223 (Xofigo®)
• Any other hormonal agent or supplement being used with the intent of cancer
treatment must be reviewed by the PI for eligibility
• External beam radiation therapy within 4 weeks of registration is prohibited, or
anticipated need for radiation therapy (e.g. imminent pathological fracture or spinal
cord compression) within 3 months of registration. Participants must have recovered
from all radiation-related toxicities and not have had radiation pneumonitis.
• Major surgery within 4 weeks of registration is prohibited
• Prior cytotoxic chemotherapy (for example, but not limited to, docetaxel,
mitoxantrone, cabazitaxel) within 28 days of registration is prohibited
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with any agent
directed to another T-cell stimulatory or inhibitory receptor (e.g. CTLA-4, OX-40,
CD137).
• Participants with a history of life-threatening autoimmune disease
• Participants with a history of non-infectious pneumonitis that required corticosteroid
treatment, or has current pneumonitis
• Participants with a history of allergic reactions to the tetanus vaccine
• Participants who have undergone splenectomy or who have a diagnosis of
immunodeficiency
• Participants must not have other active malignancies other than non-melanoma skin
cancers or superficial (non-muscle-invasive) carcinoma of the bladder. Participants
with a history of other cancers who have been adequately treated and have been
recurrence-free for > 3 years are eligible.
• Participants with known brain metastases and/or carcinomatous meningitis
• Participants who have received a live vaccine within 30 days prior to the first dose
of study drug. 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 (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not
allowed.
• Any antibiotic therapy within 1 month of day 1, or anticipated need for antibiotic
therapy within 1 month of beginning treatment
• Participants with active autoimmune disease that has required systemic treatment in
the past 2 years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.
• Any other medical intervention or condition, which, in the opinion of the PI or
treating physician, could compromise participant safety or adherence with the study
requirements (including biopsies), or confound results of the study, over the
treatment period.
• Any known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirement of the trial.
• Participants cannot have concurrent enrollment on other phase I, II, or III
investigational treatment studies.
Prostate, Castration-resistant Prostate Cancer, Metastatic Cancer, Prostate Cancer
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
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction
chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves
outcomes. This trial also studies the outcomes of patients with mixed phenotype acute
leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without
inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab,
linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in
a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy
regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin,
methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and
pegaspargase or calaspargase pegol 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 will also study the outcomes of patients with mixed phenotype acute
leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk
ALL chemotherapy.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy:
Induction and Consolidation. This part will collect information on the leukemia, as well as
the effects of the initial treatment, to classify patients into post-consolidation treatment
groups. On the second part of this study, patients with HR B-ALL will receive the remainder
of the chemotherapy cycles (interim maintenance I, delayed intensification, interim
maintenance II, maintenance), with some patients randomized to receive inotuzumab. The
patients that receive inotuzumab will not receive part of delayed intensification. Other aims
of this study include investigating whether treating both males and females with the same
duration of chemotherapy maintains outcomes for males who have previously been treated for an
additional year compared to girls, as well as to evaluate the best ways to help patients
adhere to oral chemotherapy regimens. Finally, this study will be the first to track the
outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed
Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Kenneth Desantes, M.D.
All
1 Year to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03959085
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected
MPAL patients. If not performed within this time frame, patients will be taken off
protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
every patient should be offered participation in APEC14B1. B-LLy patients may directly
enroll on AALL1732.
• Patients must be > 365 days and < 25 years of age
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on
central confirmatory testing to have B-ALL must meet the B-ALL criteria above
(age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL
stratum before the end of induction.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
paraffin blocks), the methodology and criteria for immunophenotypic analysis to
establish the diagnosis of B-LLy defined by the submitting institution will be
accepted.
• Central nervous system (CNS) status must be determined prior to enrollment based on a
sample obtained prior to administration of any systemic or intrathecal chemotherapy,
except for steroid pretreatment and cytoreduction. It is recommended that intrathecal
cytarabine be administered at the time of the diagnostic lumbar puncture. This is
usually done at the time of the diagnostic bone marrow or venous line placement to
avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic
chemotherapy must begin within 72 hours of this intrathecal therapy.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment and steroid cytoreduction or the
administration of intrathecal cytarabine, patients must not have received any prior
cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any
cancer diagnosed prior to initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of
systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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 women who plan to breastfeed their infants while on study and for 2 months
after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of study participation. For those
patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
inotuzumab ozogamicin for males.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic
alterations that have come back (recurrent) or does not respond to treatment (refractory) and
may have spread from where it first started to nearby tissue, lymph nodes, or distant parts
of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03213652
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the
presence of an actionable mutation
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment.
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on a standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively
stable for at least 7 days prior to study enrollment; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the
last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment
with other ALK inhibitors is permitted given that at least 5 half-lives or 21
days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to
enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment) (within 7 days
prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions); these patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on
age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for
female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for
female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for
female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL
for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL
for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for
female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT
is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study because there is
currently no available information regarding human fetal or teratogenic toxicities;
pregnancy tests must be obtained in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study treatment and for one week after the
last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
not eligible; if used to modify immune adverse events related to prior therapy,
>= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another
investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents
are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong
inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the
end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03155620
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and
=< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor
sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from
start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed
paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy
or surgery that was performed at any point after initial tumor recurrence/progression,
or be planned to have a procedure to obtain such a sample that is considered to be of
potential benefit by the treating clinicians; a tumor sample from a clinically
performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto
Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse
intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report
availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting
2022): In stage 2 of the study, no tumor samples will be submitted for centralized
clinical tumor profiling; instead, a tumor molecular profiling report from a College
of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments
(CLIA)-approved testing laboratory must be submitted for review by the Molecular
Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was
obtained at any point after initial tumor recurrence/progression and must be
accompanied by a pathology report for the same tumor specimen; a molecular
profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable
for enrollment onto Pediatric MATCH only for children with high-grade gliomas of
the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that
molecular profiling reports are available from multiple timepoints, the most
recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic
deficits in patients with central nervous system (CNS) tumors must have been stable
for at least 7 days prior to study enrollment; patients who are unable to walk because
of paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance
imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in
patients with CNS tumors must have been stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the performance
score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; if after the
required timeframe, the numerical eligibility criteria are met, e.g. blood count
criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be
myelosuppressive: for agents not listed, the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator prior to enrollment >= 21 days after the last dose of cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; for agents not listed, the duration of this interval
must be discussed with the study chair and the study-assigned research
coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of
antibody, and toxicity related to prior antibody therapy must be recovered
to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days
after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells,
etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not
be entered on this study due to risks of fetal and teratogenic adverse events as seen
in animal/human studies, or because there is currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Langerhans Cell Histiocytosis, Malignant Glioma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
International Registry for Men With Advanced Prostate Cancer (IRONMAN) (IRONMAN)
Our intent is to establish the International Registry to Improve Outcomes in Men with
Advanced Prostate Cancer (IRONMAN) as a prospective, international cohort of minimum 5,000
men with advanced cancer, including men with mHSPC and M0/M1 CRPC. The goal is to establish a
population-based registry and recruit patients across academic and community practices from
Australia, Barbados, Brazil, Canada, Ireland, Jamaica, Kenya, Nigeria, Norway, Spain, South
Africa, Sweden, Switzerland, the United Kingdom (UK), and the United States (US). Target
accrual number and number of participating sites are subject to change based on accrual,
funding, and interest in participation by other international sites. This cohort study will
facilitate a better understanding of the variation in care and treatment of advanced prostate
cancer across countries and across academia and community based practices.
Detailed data will be collected from patients at study enrollment and then during follow-up,
for a minimum of five years. Patients will be followed prospectively for overall survival,
clinically significant adverse events, comorbidities, changes in cancer treatments, and
PROMs.
PROMs questionnaires will be collected at enrollment and every three months thereafter.
Physician Questionnaires will be collected from all participating sites at patient
enrollment, time of first change in treatment and/or one year follow-up, at each subsequent
change of treatment, and discontinuation of treatment.
As such, this registry will help identify the treatment sequences or combinations that
optimize overall survival and PROMs for men with mHSPC and M0/M1 CRPC. By collecting blood at
enrollment, time of first change in treatment and/or one year follow-up (plasma, cell free
DNA, buffy coat / RNA), this registry will further identify and validate molecular phenotypes
of disease that predict response and resistance to specific therapeutics. Additionally, every
effort will be made to collect blood specimen at each subsequent change in treatment due to
progression of disease. When feasible, existing tumor tissue may be collected for correlation
with described blood based studies. All samples will be used for future research. This cohort
study will provide the research community with a unique biorepository to identify biomarkers
of treatment response and resistance.
Hamid Emamekhoo, M.D.
Male
21 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03151629
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• Willing and able to provide written informed consent and privacy authorization for the
release of personal health information.
NOTE: Privacy authorization may be either included in the informed consent or obtained
separately.
• Males 21 years of age and above
• Histological or cytological confirmed prostate adenocarcinoma from TRUS biopsy,
radical prostatectomy or TURP Or Documented histopathology or cytopathology of
prostate adenocarcinoma from a biopsy of a metastatic site Or Metastatic disease
typical of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic
lymph nodes) AND a serum concentration of PSA >20ng/mL at the time of initial prostate
cancer diagnosis
• No previous diagnosis of a second, non-prostate malignancy that requires additional
systemic therapy except cancer in situ of bladder and basal cell cancer of skin
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
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
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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
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
Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer
The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with
T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen
deprivation in patients with newly diagnosed prostate cancer scheduled to undergo
prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a
pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy,
will be invited to participate and will be on study for up to 15 months.
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04989946
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Inclusion Criteria:
• Histologically confirmed adenocarcinoma of the prostate
• Patients must be considered candidates for prostatectomy as per standard of care
• High-risk patients for recurrent disease, with high risk defined based on one of the
following criteria:
• Gleason score 7 and baseline serum prostate specific antigen (PSA) > 20 ng/mL
• Gleason score > 7
• Life expectancy of at least 12 months at screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, renal and liver function as evidenced by the following within 4
weeks of day 1:
• Absolute neutrophil count (ANC) > 1000 / mm3
• HgB > 9.0 gm/dL independent of transfusion
• Platelets > 100,000 / mm3
• Creatinine < 2.0 mg/dL
• Aspartate aminotransferase (AST), Alanine transaminase (ALT) < 2.5 x
institutional upper limit of normal (ULN)
• Total bilirubin < 2x institutional ULN (NOTE: in subjects with Gilbert's
syndrome, if total bilirubin is >2x ULN, measure direct and indirect bilirubin
and if direct bilirubin is within normal range, subject may be eligible)
• No known history of HIV 1 and 2, HTLV-1, or active Hepatitis B or Hepatitis C
• Must have adequate tissue (ten 5µm unstained formalin-fixed paraffin-embedded (FFPE)
sections containing prostate cancer) remaining from pre-treatment diagnostic prostate
biopsy for research purposes
• Patients must be willing to undergo large-volume blood draws (up to 200mL per time
point) for the investigational component of this trial
• For those patients who are sexually active, they must be willing to use barrier
contraceptive methods during the period of treatment on this trial
• Patients must be informed of the experimental nature of the study and its potential
risks, and must sign an IRB-approved written informed consent form indicating such an
• Ability to comply with all study procedures and willingness to remain supine for 120
minutes during imaging
Exclusion Criteria:
• Small cell or other variant (non-adenocarcinoma) prostate cancer histology
• Prior treatment for prostate cancer, including androgen deprivation therapy (ADT),
orchiectomy, antiandrogens, ketoconazole, abiraterone acetate or enzalutamide
• Prior radiation to the prostate
• Patients may not be receiving other investigational agents or be receiving concurrent
anticancer therapy other than the treatment-prescribed androgen deprivation therapy
• Treatment with any of the following medications while on study is prohibited, washout
period not required except as indicated:
• Systemic corticosteroids (at doses over the equivalent of 10 mg prednisone daily)
•not permitted within 3 months of registration; inhaled, intranasal or topical
corticosteroids are acceptable
• PC-SPES
• Herbal supplements that have been shown to modulate testosterone or androgen
signaling (e.g. Saw Palmetto) are not allowed while on study
• Megestrol
• Ketoconazole
• 5-α-reductase inhibitors •patients already taking 5-α-reductase inhibitors prior
to 28 days prior to registration may stay on these agents throughout the course
of therapy, but these should not be started while patients are on study
• Diethylstilbesterol
• Any other non-study hormonal agent or supplement being used with the intent of
cancer treatment
• Major surgery within 4 weeks of registration is prohibited
• Active cardiac disease defined as active angina, symptomatic congestive heart failure,
or myocardial infarction within 6 months of registration
• Patients with known psychological or sociological conditions, addictive disorders or
family problems, which would preclude compliance with the protocol
• Patients who have undergone splenectomy
• Patients must not have other active malignancies other than non-melanoma skin cancers
or carcinoma in situ of the bladder, that have been adequately treated. Subjects with
a history of other cancers who have been adequately treated and have been
recurrence-free for > 3 years are eligible.
• Any other medical intervention or condition, which, in the opinion of the principle
investigator (PI) or treating physician, could compromise patient safety or adherence
with the study requirements over the primary 3-6 month treatment period.
• Patients who have concurrent enrollment on other phase I, II, or III investigational
treatment studies cannot be actively receiving treatment and the last dose cannot be
within 4 weeks.
• Patients who have received a live vaccine within 14 days prior to the first dose of
study treatment. 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 (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not
allowed
• Patients with a history of life-threatening autoimmune disease or active autoimmune
disease that has required systemic treatment in the past 2 years (i.e. with use of
disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement
therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment
• Patients with a history of non-infectious pneumonitis that required corticosteroid
treatment, or has current pneumonitis
• Patients with a history of allergic reactions to the tetanus vaccine
Impact of DNA Repair Pathway Alterations on Sensitivity to Radium-223 in Bone Metastatic Castration-resistant Prostate Cancer
This study investigates how well radium-223 works in treating patients with
castration-resistant prostate cancer than has spread to the bones (bone metastases). Prostate
cancer is the most common cancer in men and the second leading cause of cancer death.
Furthermore, many men with notably advanced disease have been found to have abnormalities in
DNA repair. The purpose of this research is to study the role of a DNA repair pathway in
prostate cancer, specifically in response to administration of radium-223, an FDA-approved
drug known to cause DNA damage to cancerous cells. Understanding how defects in the DNA
repair pathway affects radium-223 treatment of prostate, may help doctors help plan effective
treatment in future patients.
Glenn Liu, MD
Male
18 Years and over
II
This study is NOT accepting healthy volunteers
NCT04489719
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Inclusion Criteria:
• Patient must be >= 18 years of age
• Patient must have histopathologic diagnosis of prostate cancer
• Patient must have castration-resistant prostate cancer
• Patient must have radiographic evidence of bone metastasis
• Patients must be symptomatic from prostate cancer
• Patient must have plans to undergo treatment with radium-223
• Patient must have a PSA level >= 10 ng/mL
• Patient must have castrate testosterone levels demonstrated within the last 3 months
prior to screening
• Patient must have anticipated survival > 3 months
• Patient must be willing and able to authorize consent
• Patient must be willing and able to comply with the protocol, including follow-up
visits
Exclusion Criteria:
• Patient must not have visceral metastasis
• Patients on regimens of radium-223 in combination with other antineoplastic agents are
excluded
* Bone-targeted only therapy (e.g. denosumab or zoledronic acid) will be allowed
• Patients who have received prior radium-223
• Patients who have received prior platinum containing chemotherapy
• Absolute neutrophil count (ANC) < 1.5 x 10^9/L
• Hemoglobin (HB) < 9 g/dL
• Platelets (PLT) < 100 x 10^9/L
• Any condition which, in the investigator's opinion, makes the subject unsuitable for
trial participation
Castration-Resistant Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Prostate
A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer
A Phase 1/2 study to evaluate the safety and efficacy of ARV-766 given by mouth alone or in
combination with abiraterone in men with metastatic prostate cancer.
Joshua Lang, Post Grad
Male
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05067140
Show full eligibility criteria
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Inclusion Criteria:
Part A,B,C and D:
• Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of
the prostate.
• Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone
analog or inhibitor, or orchiectomy (surgical or medical castration).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Part A:
• Progression on at least 2 prior approved systemic therapies for metastatic prostate
cancer (at least one must be a second-generation androgen inhibitor, e.g.,
abiraterone, enzalutamide, darolutamide, apalutamide).
• Progressive mCRPC
Part B:
• Participants must have received at least one but no more than three prior second
generation anti-androgen agents (e.g., enzalutamide or abiraterone).
• Participants must have received no more than two prior chemotherapy regimens.
• Progressive mCRPC
Part C & D:
• Metastatic castration resistant or sensitive prostate cancer with radiographic evidence
of metastatic disease
Exclusion Criteria:
Part A and B:
• Known symptomatic brain metastases requiring steroids (above physiologic replacement
doses).
• Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular
disease, or previous gastric resection or lap band surgery.
• Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to
>25% of the bone marrow.
• Receipt of an investigational drug(s) within 4 weeks prior to anticipated first dose
• Systemic anti-cancer therapy within 2 weeks of first dose of study drug (except agents
to maintain castrate status). For bicalutamide, mitomycin C, or nitrosoureas the
exclusion period must be 6 weeks and for abiraterone 4 weeks.
Part C and D
• Prior treatment with a second generation NHA
EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC
This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in
subjects with mCRPC.
Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination
with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the
safety and tolerability of the drug combination and establish the RP2CDs for EPI-7386 and
enzalutamide when dosed in combination. In addition, blood sampling will be conducted for PK
evaluation to assess the potential DDI between the two drugs.
Once the RP2CD for each drug has been established, Phase 2 of the study will commence. Phase
2 is a two-arm, randomized (2:1), open-label study. Approximately 120 subjects will be
randomized 2:1 to:
- Group 1: EPI-7386 at the RP2CD + enzalutamide(depending on the results of the Phase 1)
(n=80)
- Group 2: Enzalutamide single agent (n=40) The planned dose of enzalutamide and EPI-7386
for the combination arm will be those determined in the Phase 1 of this study based on
safety and exposure data. Subjects may remain on study treatment as long as they are
tolerating treatment without disease progression based on RECIST v1.1 and/or PCWG3.
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05075577
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Inclusion Criteria:
• Males ≥18 years.
• Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on
bone scan or by soft tissue disease observed by CT/MRI.
• Naïve to second generation anti-androgens.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3
(PCWG3) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist
therapy or history of bilateral orchiectomy, with castrate level testosterone.
• Serum testosterone ≤1.73 nmol/L (50 ng/dL).
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g.,
denosumab) must be on a stable dose for at least 28 days prior to the start of study
treatment.
• Demonstrate adequate organ function.
Exclusion Criteria:
• Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days
prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that
may have hormonal anti-prostate cancer activity within 28 days prior to the start of
study treatment or plans to initiate during the study.
• Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs
within 28 days of the first dose of study treatment.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days
prior to the start of study treatment.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any
radiotherapy within 2 weeks prior to the start of study treatment.
• Received a blood transfusion within 28 days of hematologic screening labs.
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable
for the last 28 days before signing of informed consent.
• Spinal cord compression.
• Diagnosis of another clinically significant malignancy within the previous 3 years
other than curatively treated non-melanomatous skin cancer or superficial urothelial
carcinoma and other in situ or non-invasive malignancies.
• Gastrointestinal issues affecting absorption.
• Significant cardiovascular disease.
• Known history of seizure or conditions that may pre-dispose them to seizure, including
brain injury with loss of consciousness, transient ischemic attack within the past 12
months, cerebral vascular accident, brain metastases, and brain arteriovenous
malformation.
• Concurrent disease or any clinically significant abnormality.
• Known or suspected hypersensitivity to any components of the formulation used for
EPI-7386 or enzalutamide.
• Use of strong inhibitors of CYP2C8.
• Use of strong inducers of CYP3A.
• Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and
CYP2B6.
• Use of granulocyte colony stimulating factor within 7 days prior to screening
laboratories.
• Not a candidate for enzalutamide treatment.
• Patients with rare hereditary problems of fructose intolerance.
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.
Advanced 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, 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
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
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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
Nivolumab + Docetaxel + ADT in mHSPC Patients With DDRD or Inflamed Tumors
This research study is studying a combination of hormonal therapy, chemotherapy, and
immunotherapy as a possible treatment for metastatic hormone-sensitive prostate cancer. The
names of the study drugs involved in this study are:
- Androgen deprivation therapy (ADT) with a drug of your physician's choice. This may
include leuprolide (Lupron), goserelin acetate (Zoladex), or degarelix (Firmagon).
- Docetaxel
- Nivolumab
Hamid Emamekhoo, M.D.
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04126070
Show full eligibility criteria
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Inclusion Criteria:
• Newly diagnosed histologically confirmed prostate adenocarcinoma within 6 months prior
to study registration with evidence of high-volume distant metastasis on conventional
imaging
• Distant metastasis is defined by non-regional lymph node(s) metastasis (M1a), bone
metastasis (M1b), and/or other site(s) of metastatic disease (M1c).
• Conventional imaging consists of CT, MRI or radionuclide bone scan
• High volume of disease is defined by presence of four or more bone lesions with at
least one beyond the vertebral bodies or pelvis or any site of visceral metastasis.
• Age ≥18 years
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Subjects with ECOG performance status of 2 are only eligible if the performance status
decline is attributed to metastatic prostate cancer
• Serum PSA > 4.0 ng/mL before initiation of ADT
• Serum testosterone > 100 ng/dL before initiation of ADT
• Subjects whose testosterone level is unknown before initiation of ADT may be allowed
after discussion with Sponsor-Investigator.
• Grade ≤ 1 peripheral neuropathy, defined as asymptomatic or paresthesia and/or
decreased deep tendon reflexes is allowed.
• Subjects must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500 /mcL
• Platelets ≥100,000 /mcL
• Total bilirubin ≤1.5 × institutional upper limit of normal. Exception: Subjects
with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia
that is predominantly unconjugated in the absence of hemolysis or hepatic
pathology) may be allowed after consultation with treating physician
• AST(SGOT) and ALT(SGPT) ≤2.5 × institutional upper limit of normal. Exception: ≤5
x institutional upper limit of normal in subjects with liver metastasis
• Creatinine (Cr) and creatinine clearance (CrCl) Cr <1.6 mg/dL or CrCl ≥30 mL/min;
CrCl should be calculated using the Cockcroft-Gault formula: CrCl (mL/min) =
(140-Age) x Body weight (Kg)/72 x Serum creatinine (mg/dL)
• PT, INR and PTT ≤ 1.5 x institutional upper limit of normal. Exception: Subjects
who are on a stable regimen of therapeutic anticoagulation for an appropriate
clinical indication may be enrolled
• Availability of adequate baseline prostate biopsy tissue for integral biomarker
analysis and correlative studies:
• Sources of tumor tissue allowed are (1) prostate biopsy, (2) transurethral
resection of the prostate tissue (TURP) , (3) trans urethral resection of bladder
tumor tissue (TURBT) with contiguous spread of prostate cancer to the bladder,
and (4) metastatic biopsy tissue excluding bone and lymph node metastases (e.g.
lung or liver biopsies are acceptable).
• For OncoPanel, submit at least one (1) H&E slide and ten (10) 5-micron thick
serially sectioned unstained formalin-fixed paraffin-embedded (FFPE) slides.
Biopsy should contain at least 20% tumor involvement with the highest Gleason
score(s). If requested tissue is unavailable, a lower number of 4-micron or 5-
micron slides and/or slides containing lower tumor involvement may be accepted
after discussion with the Sponsor-Investigator.
• For ImmunoProfile, submit at least one (1) H&E slide and one (1) 5-micron thick
serially sectioned unstained, freshly cut, FFPE slide. Biopsy should contain at
least 50% tumor involvement with the highest Gleason score(s). If requested
tissue is unavailable, a 5-micron slide containing lower tumor involvement may be
accepted after discussion with the study Sponsor-Investigator.
• Submission of one (1) H&E slide and at least one (1) FFPE tissue core block with
at least 3mm2 tumor area with the highest Gleason score is an acceptable
alternative to unstained FFPE slides.
• Subjects who have insufficient baseline prostate biopsy tissue for OncoPanel
analysis but have baseline metastatic biopsy tissue available may have OncoPanel
analysis performed using metastatic biopsy tissue. Successful OncoPanel testing
(but not ImmunoProfile) of metastatic biopsy tissue is acceptable from any source
including lymph node or bone, after discussion with the study Sponsor-
Investigator.
• For Exploratory Correlative Studies, at least 1 tissue core block (preferred) or
one (1) H&E slide and twelve (12) 5-micron thick FFPE slides with unstained,
freshly cut, serial sections from biopsy cores containing at least 20% tumor
involvement with the highest Gleason score(s) will be requested, if available.
• Tissue should be submitted with redacted pathology report.
• Successful OncoPanel and ImmunoProfile biomarker analysis for allocation into a study
cohort during pre-screening
• Subjects whose tumors harbor somatic or germline homozygous deletions and/or
deleterious mutations in a DDR gene using OncoPanel will be assigned to Cohort 1,
regardless of ImmunoProfile results
• DDR genes include and are not limited to BRCA2, ATM, CHEK2, BRCA1, PALB2, RAD51D,
ATR, NBN, PMS2, GEN1, MLH1, MSH2, MSH6, RAD51C, MRE11A, BRIP1, FAM175A, and CDK12
• Deleterious mutations are defined as loss of function, splice site, nonsense, or
frameshift mutations, and determination will be made between DFCI molecular
pathology and study Sponsor-Investigator
• Tumors identified as mismatch repair deficient (MMR-d) or microsatellite
instability high (MSI-H) will also be included in Cohort 1
• Patients with germline DDRD or MMR-d/MSI-H (Lynch Syndrome) or tumors with DDRD
or MMR-d/MSI-H identified in another CLIAcertified laboratory (e.g., Foundation
Medicine) using prostate or metastatic tissue may be assigned to Cohort 1 after
discussion with the Sponsor-Investigator. If archival tissue is available, it
will be requested for OncoPanel testing; however, results will not influence
eligibility.
• Subjects whose tumors are PD-L1 positive and/or CD8+ T cell inflamed using
ImmunoProfile without the presence of DDRD will be assigned to Cohort 2
• PD-L1 positivity will be defined as Combined Positive Score (CPS) ≥ 1, which is
the number of PD-L1 staining cells (e.g., tumor cells, immune cells) divided by
the total number of tumor cells, multiplied by 100
• CD8+ T cell inflammation will be defined as CD8+ T cell density ≥ 200, which is
the number of CD8+ cells divided by the surface area of a region of interest
(mm2)
• Subjects whose tumors do not harbor DDRD and are PD-L1 negative with low CD8+ T
cell infiltration will be assigned to Cohort 3
• Subjects whose prescreening is unsuccessful for cohort allocation or whose
biomarker status matches that of a filled cohort will not be eligible
• Subjects who underwent successful ImmunoProfile pre-screening but failed
OncoPanel pre-screening may be allocated to Cohort 2 or Cohort 3 based on
ImmunoProfile results and assuming DDRD negativity, at the discretion of the
Sponsor-Investigator.
• Before one of the study cohorts enrolls 15 of 20 subjects (Cohort 3 is
anticipated to complete accrual first), subjects may undergo main study screening
when ImmunoProfile and OncoPanel analyses are ongoing, and may proceed to study
treatment if they meet all eligibility criteria with the exception that OncoPanel
analysis is ongoing. These patients will be allocated into their respective
cohort after OncoPanel results return.
• Willingness to provide leftover metastatic biopsy tissue for correlative studies, if
obtained for clinical purposes
• Based on its mechanism of action and data from animal studies, nivolumab can cause
fetal harm. For this reason non-sterilized men who are sexually active with a female
partner of childbearing potential treated or enrolled on this protocol must agree to
use adequate contraception prior to the study, for the duration of study
participation, and for 7 months after last dose of nivolumab administration
• Adequate contraception includes male condom plus spermicide
• Not engaging in sexual activity is an acceptable practice; however, occasional
abstinence, the rhythm method, and the withdrawal method are not acceptable
methods of contraception
• Subjects in this study should refrain from sperm donation
• Ability to understand and the willingness to sign a written informed consent document,
or have a legally authorized representative sign on the subject's behalf
Exclusion Criteria:
• Subjects must not have received prior ADT (LHRH analogue +/- antiandrogen),
chemotherapy, or immunotherapy for prostate cancer. The following exception is
allowed:
• Subjects who have initiated ADT prior to study registration and are able to
complete biomarker pre-screening, cohort allocation, and start C1D1 study
chemoimmunotherapy ≤120 days from initiation of ADT are allowed
• The 120-day window commences at the start of either the antiandrogen agent or
LHRH analogue, whichever is earlier
• Antiandrogens (e.g., bicalutamide or flutamide) may be used in addition to LHRH
analogue ≤60 days before initiation of LHRH analogue to cover the testosterone
surge associated with certain LHRH agonists but must be discontinued prior to
study registration
• Second-generation hormonal agents (e.g., abiraterone acetate) are not allowed
• Subjects must not have undergone prostatectomy
• Prostate radiation is allowed before or after study enrollment and may be
delivered concurrently with study chemoimmunotherapy, per provider discretion,
assuming adequate prostate biopsy tissue is collected before prostatic radiation
• Metastasis-directed radiation is allowed before or after study enrollment and may
be delivered concurrently with study chemoimmunotherapy, per provider discretion
• Subjects who are receiving any other investigational agents
• Any previous treatment with a PD-1 or PD-L1 inhibitor
• Subjects with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other AEs
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to docetaxel (including any drugs formulated with polysorbate 80),
nivolumab, or LHRH analogue (e.g., leuprolide, goserelin acetate, degarelix)
• History of another primary malignancy, except for:
• Malignancy treated with curative intent and with no known active disease for ≥2
years before the first dose of study treatment and of low potential risk for
recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
• Major surgical procedure as defined by the Site Investigator within 28 days prior to
the first dose of chemoimmunotherapy
• Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome. HIV-positive subjects on combination
antiretroviral therapy are ineligible because of the potential for nivolumab to be
less clinically active in this population. In addition, these subjects are at
increased risk of lethal infections when treated with marrow-suppressive chemotherapy
• History of allogeneic bone marrow or organ transplantation
• Active or prior documented autoimmune or inflammatory disorders, including=
inflammatory bowel disease (e.g., Crohn's disease), systemic lupus erythematosus,
Sarcoidosis syndrome, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis,
with the following exceptions:
• Vitiligo or alopecia
• Hypothyroidism stable on hormone replacement
• Chronic skin condition that does not require systemic therapy
• Celiac disease controlled by diet alone
• Subjects with inactive disease in the last 5 years may be included but only after
consultation with the study physician
• Active infection including tuberculosis, hepatitis B (known positive HBV surface
antigen [HBsAg]), or hepatitis C (HCV)
• Subjects with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible
• Subjects with positive HCV antibody are eligible if polymerase chain reaction is
negative for HCV RNA
• Concurrent or prior use of immunosuppressive medication within 14 days before the
first dose of study chemoimmunotherapy, with the following exceptions:
• Premedication for docetaxel with oral dexamethasone (See Section 5.1)
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intraarticular injection)
• Systemic corticosteroids at physiologic doses not exceeding 10mg/day of
prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., premedication for
iodinated contrast allergy before CT scan)
Inclusion of Minorities
• Men of all races and ethnic groups are eligible for this trial.
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
Imaging and Genomic Biomarkers to Predict Response in Prostate Cancer
The purpose of this study is to evaluate the imaging and gene expression biomarkers in
prostate cancer. Participants have high-risk prostate cancer and have indicated they will
undergo external beam radiation therapy, brachytherapy, and androgen deprivation therapy
(EBRT+BTX+ADT). Participants can expect to be in this study for up to 5 years.
John Floberg, Assistant Professor
All
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT05477823
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Inclusion Criteria:
• Age ≥ 18
• Histologically confirmed adenocarcinoma of the prostate
• Cancer classified as high-risk or very high-risk by National Comprehensive Cancer
Network (NCCN) criteria: Grade group ≥4, PSA >20, or primary tumor stage ≥T3a
• ECOG performance status 0-1
• Agreed to undergo EBRT, high dose rate (HDR) brachytherapy boost, and 6-36 months of
ADT as part of standard of care therapy prior to study enrollment
• Able to undergo a HDR brachytherapy implant: Pre-radiation IPSS score ≤20 with or
without medical management; prostate ≤60 cc as measured by MRI or ultrasound; no prior
trans-urethral resection of prostate (TURP); and, median lobe extending into the
bladder <1 cm
• No prior or concurrent malignancy unless disease-free for at least 5 years
Exclusion Criteria:
• Evidence of regional or distant metastatic disease on pre-treatment bone scan, pelvic
MRI, and/or CT of the abdomen/pelvis
• Prior pelvic radiation therapy
Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score
This phase III trial uses the Decipher risk score to guide intensification (for higher
Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better
match therapies to an individual patient's cancer aggressiveness. The Decipher risk score
evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk
scores, this trial compares radiation therapy alone to the usual treatment of radiation
therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high
energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation
therapy blocks the production or interferes with the action of male sex hormones such as
testosterone, which plays a role in prostate cancer development. Giving radiation treatment
alone may be the same as the usual approach in controlling the cancer and preventing it from
spreading, while avoiding the side effects associated with hormonal therapy. In patients with
higher Decipher gene risk, this trial compares the addition of darolutamide to usual
treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the
actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition
of darolutamide to the usual treatment may better control the cancer and prevent it from
spreading.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05050084
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of
the prostate within 270 days prior to registration
• Unfavorable intermediate risk prostate cancer, defined as having ALL the following
bulleted criteria:
• Has at least one intermediate risk factor (IRF):
• PSA 10-20 ng/mL
• Clinical stage T2b-c (digital rectal examination [DRE] and/or imaging) by
American Joint Committee on Cancer (AJCC) 8th edition
• Gleason score 7 (Gleason 3+4 or 4+3 [ International Society of Urological
Pathology (ISUP) Grade Group 2-3])
• Has ONE or more of the following 'unfavorable' intermediate-risk designators:
• > 1 immature reticulocyte fraction (IRF)
• Gleason 4+3=7 (ISUP Grade Group 3)
• >= 50% of biopsy cores positive
• Biopsies may include 'sextant' sampling of right/left regions of the
prostate, often labeled base, mid-gland and apex. All such 'sextant'
biopsy cores should be counted. Men may also undergo 'targeted'
sampling of prostate lesions (guided by MRI, ultrasound or other
approaches). A targeted lesion that is biopsied more than once and
demonstrates cancer (regardless of number of targeted cores involved)
should count as a single additional positive core sampled and positive.
In cases of uncertainty, count the biopsy sampling as sextant core(s)
• Absence of high-risk features
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 120 days prior to registration;
• Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m
bone scan or sodium fluoride (NaF) positron emission tomography (PET) are
allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed
tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis
at the concerned site(s). While a negative fluciclovine, choline, or prostate
specific membrane antigen (PSMA) PET may be counted as acceptable substitute for
bone imaging, any suspicious findings must be confirmed and correlated with
conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine
eligibility based on the latter modalities (e.g. M0 based on conventional imaging
modalities)
• Clinically negative lymph nodes (N0) as established by conventional imaging
(pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients
with lymph nodes equivocal or questionable by imaging are eligible if the nodes
are =< 1.0 cm in short axis and/or if biopsy is negative.
Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA)
PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings
must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet
pathological criteria based on the latter modalities (e.g. node =< 10 mm in short axis,
negative biopsy), the patient will still be eligible
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days
prior to registration
• Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration
• Absolute neutrophil >= 1,000 cells/mm^3 (within 120 days prior to registration)
• Hemoglobin >= 8.0 g/dL, independent of transfusion and/or growth factors (within 120
days prior to registration)
• Platelet count >= 100,000 cells/mm^3 independent of transfusion and/or growth factors
(within 120 days prior to registration)
• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within
120 days prior to registration)
• For African American patients specifically whose renal function is not considered
adequate by the formula above, an alternative formula that takes race into
account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula)
should be used for calculating the related estimated glomerular filtration rate
(GFR) with a correction factor for African American race creatinine clearance for
trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin: 1.5 =< institutional upper limit of normal (ULN) (within 120 days
prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin
is > 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less
than or equal to 1.5 x ULN, subject is eligible)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x
institutional ULN (within 120 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial;
Note: HIV testing is not required for eligibility for this protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy. Patients who are
immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible
(e.g. patients immunized against hepatitis B)
• For 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
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Previous radical surgery (prostatectomy) or any form of curative-intent ablation
whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound
[HIFU], laser thermal ablation, etc.) for prostate cancer
• Definitive clinical or radiologic evidence of metastatic disease (M1)
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is
not allowed
• Prior radiotherapy to the prostate/pelvis region that would result in overlap of
radiation therapy fields
• Previous bilateral orchiectomy
• Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH)
agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist
(e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate).
ADT started prior to study registration is not allowed
• Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped
prior to enrollment on the study with at least a 30 day washout period before baseline
study PSA measure and registration
• Active testosterone replacement therapy; any replacement therapy must be stopped at
least 30 days prior to registration
• Severe, active co-morbidity defined as follows:
• Current severe or unstable angina;
• New York Heart Association Functional Classification III/IV (Note: Patients with
known history or current symptoms of cardiac disease, or history of treatment
with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification)
• History of any condition that in the opinion of the investigator, would preclude
participation in this study
• Inability to swallow oral pills
• High risk features, which includes any of the following:
• Gleason 8-10 [ISUP Grade Group 4-5]
• PSA > 20
• cT3-4 by digital exam OR gross extra-prostatic extension on imaging
[indeterminate MRI evidence will not count and the patient will be eligible]
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
Show full eligibility criteria
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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
Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of
Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination with Anticancer Agents in
Patients with Advanced/Metastatic Solid Tumours.
Joshua Lang, Post Grad
All
18 Years to 130 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT05489211
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Key
Inclusion Criteria:
• Male and female, ≥ 18 years
• Documented advanced or metastatic malignancy
• Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration
over the 2 weeks prior to baseline or day of first dosing
• All participants must provide a tumour sample for tissue-based analysis
• At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate
Cancer) which allows participants with non measurable bone metastatic disease
• Adequate bone marrow reserve and organ function
• Minimum life expectancy of 12 weeks
• At the time of screening, contraceptive use by men or women should be consistent with
local regulations regarding the methods of contraception for those participating in
clinical studies
• All women of childbearing potential must have a negative serum pregnancy test
documented during screening
• Female participants must be 1 year post-menopausal, surgically sterile, or using 1
highly effective form of birth control. Female participants must not donate, or
retrieve for their own use, ova at any time during this study
• Male participants who intend to be sexually active with a female partner of
childbearing potential must be surgically sterile, avoid intercourse, or use a highly
effective method of contraception. Male participants must not freeze or donate sperm
at any time during this study.
• Capable of giving signed informed consent
• Provision of signed and dated written optional genetic research informed consent prior
to collection of samples for optional genetic research that supports the Genomic
Initiative
Key
Exclusion Criteria:
• Any evidence of diseases which, in the investigator's opinion, makes it undesirable
for the participant to participate in the study or that would jeopardize compliance
with the protocol
• History of another primary malignancy except for adequately resected basal cell
carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy
treated with curative intent
• Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not
yet improved
• Spinal cord compression or brain metastases unless treated
• Leptomeningeal carcinomatosis
• Clinically significant corneal disease
• Active hepatitis or uncontrolled hepatitis B or C virus infection
• Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for
example prodromal symptoms
• Known HIV infection that is not well controlled
• Active TB infection
• Significant cardiac diseases
• History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required
steroids
• Has severe pulmonary function compromise
• Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout
period
• Receipt of live, attenuated vaccine within 30 days prior to the first dose of study
intervention
• Prior exposure to anticancer therapies without an adequate treatment washout period
prior to enrolment or any concurrent anticancer treatment
• Major surgical procedure or significant traumatic injury within ≤ 3 weeks of the first
dose of study intervention or an anticipated need for major surgery during the study
• Prior treatment with TROP2-directed Anti-drug antibody, ADC Antibody-drug conjugate
(ADCs), other ADCs with deruxtecan payload
• Severe hypersensitivity to monoclonal antibodies
• Pregnant, breastfeeding, planning to become pregnant
Esophagus, Stomach, Colon, Rectum, Other Digestive Organ, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Colon and Rectum, Gastrointestinal cancers, other, Genitourinary cancers, other, Uterus, Endometrial Cancer, Gastric Cancer, Metastatic Castration-resistant Prostate Cancer, Ovarian Cancer, Colorectal Cancer, Urothelial Cancer, Biliary Tract Cancer
Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
This phase II trial tests whether nivolumab in combination with cabozantinib works in
patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking
some of the enzymes needed for cell growth. It works by blocking the action of an abnormal
protein that signals tumor cells to multiply. This helps stop the spread of tumor cells.
Giving nivolumab in combination with cabozantinib could prevent cancer from returning.
Vincent Ma, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05111574
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Inclusion Criteria:
• STEP 0 INCLUSION CRITERIA
• Histologically proven mucosal melanoma by local pathology
• Central PD-L1 tumor tissue submission
• STEP 1 INCLUSION CRITERIA
• Receipt of the central PD-L1 testing results available
• Disease status-Resected R0 or R1 disease patients. Patients eligible for randomization
have resected R0 or R1 disease (with negative margins or positive microscopic margins)
that must meet one of the following 4 criteria as defined below:
• Regional lymph node (LN) involvement; OR
• In-transit metastases/satellite primary disease; OR
• Single localized, primary disease meeting one of the following site-specific
requirements:
• Head/neck •Sinonasal (including nasopharynx): any primary lesion; Nasal or
oral cavity; pT4a or above, given slightly improved OS
• NOTE: Conjunctival: does not meet the qualification for eligibility
• Anorectal •any primary lesion
• Vaginal/cervical •any primary, as they have 5 year OS rates of 5-25
• Urinary tract •any primary urethral or bladder tumor
• Penile
• Vulvar- AJCC cutaneous stage IIB or higher
• Esophageal/gallbladder •any primary
• Locoregionally recurrent following prior resection, meeting at least one of the
above criteria
• In addition, patients must have undergone cross-sectional imaging of the brain,
chest, abdomen and pelvis with no evidence of distant metastatic disease
• Disease status-Non-resected R2 or metastatic disease patients
• Non-resected R2 or metastatic disease that is assessable and measurable
radiographically or by physical examination
• Prior Treatment:
• No prior systemic checkpoint inhibitor therapy of mucosal melanoma, including in
the adjuvant setting, is allowed. Prior adjuvant chemotherapy or interferon is
allowed.
• No other active, concurrent malignancy that requires ongoing systemic treatment
or interferes with radiographic assessment of melanoma response as determined by
the investigator. Exceptions may allow for adjuvant no evidence of disease (NED)
cancers undergoing hormone based therapy may be eligible pending the other
eligibility criteria are met and the principal investigator (PI) affirms the
hormonal agent would not change the melanoma response.
• Any radiation must have completed 28 days prior to randomization and the patient
must have adequately recovered from its effects.
• For resectable patients only: Surgery must have completed 28 days prior to
randomization.
• For resectable patients only: Surgery must have completed no more than 84 days
prior to randomization.
• Not pregnant and not nursing, because this study has an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative pregnancy test done =< 7 days prior to registration is
required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >=
50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Albumin >= 2.8 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
• No cardiovascular disease, including:
• No history of acute coronary syndromes (including myocardial infarction and
unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or
stenting within 6 months prior to study entry.
• No history of current class II or higher congestive heart failure as defined by
the New York Heart Association (NYHA) functional classification system.
• No refractory hypertension defined as a blood pressure of systolic > 140 mmHg
and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive
therapy.
• No history of myocarditis.
• No history of syncope of cardiovascular etiology, uncontrolled cardiac
arrhythmia, history of Mobitz II second degree or third degree heart block
without a permanent pacemaker in Association (NYHA) class II to IV heart failure,
or stroke/transient ischemic attack (TIA) within the past 3 months.
• No corrected QT interval by Fridericia's formula (QTcF) > 500 msec. Note: if
initial QTcF is found to be > 500 ms, two additional EKGs separated by at least 3
minutes should be performed. If the average of these three consecutive results
for QTcF is =< 500 ms, the subject meets eligibility in this regard.
• No underlying hematologic issues, including:
• Congenital bleeding diathesis
• Gastrointestinal (GI) bleeding requiring intervention within the past 6 months,
unless directly related to mucosal melanoma
• Active hemoptysis within 42 days prior to study enrollment.
• Active tumor lesions with cavitations or tumor lesions which invade, encase, or
abut major blood vessels. The anatomic location and characteristics of primary
tumors or metastases as well as the medical history should be carefully reviewed
in the selection of subjects for treatment with cabozantinib/placebo.
• Pulmonary emboli or deep vein thromboses (DVT) that require an active
anticoagulation regimen.
• No known or suspected history of cytopenia (low white blood cell [WBC],
hemoglobin or platelet count) of greater than 3 months duration with an unknown
cause, myelodysplastic syndrome, or hematologic malignancies.
• No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or
viral infection requiring treatment at the time of pre-registration (e.g., active
symptoms of COVID-19 infection or a post-infectious symptomatic autoimmune syndrome,
serious bacterial infections requiring antibiotics).
• No known or suspected gastrointestinal disorder affecting absorption of oral
medications.
• Comorbid conditions:
• No active autoimmune disease or any condition requiring systemic treatment with
either corticosteroids (> 10 mg daily of prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration.
Inhaled or topical steroids and adrenal replacement doses > 10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease.
• No history of autoimmune motor neuropathy (e.g., Guillain-Barre syndrome,
myasthenia gravis) or non-infectious pneumonitis.
• No history of severe allergic reactions to an unknown allergen or any components
of the study drugs or its excipients.
• No history of gastrointestinal perforation or abdominal fistula.
• No clinically suspected central nervous system (CNS) (leptomeningeal or
parenchymal) metastases. Patients with a history of CNS metastasis(s) will be
allowed as long as
• The metastatic site(s) were adequately treated as demonstrated by clinical
and radiographic improvement, AND
• The patient has recovered from the intervention (no residual adverse events
> Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND
• The patient has remained without occurrence of new or worsening CNS symptoms
for a period of 28 days prior to enrollment.
• No history of seizure or any condition that may increase the patient's seizure
risk (e.g., prior cortical stroke, significant brain trauma) within 2 years.
• No clinically active or chronic liver disease resulting in moderate/severe
hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding
due to liver dysfunction.
• No untreated spinal cord compression or evidence of spinal metastases with a risk
of impending fracture or spinal cord compression. Spinal metastases must have
completed planned radiation or surgical therapy prior to registration.
• Concomitant medications:
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on
this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 5
days prior to the start of study treatment.
• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed.
Patients must discontinue the drug 5 days prior to the start of study treatment.
Anal Melanoma, Bladder Melanoma, Cervical Melanoma, Esophageal Melanoma, Gallbladder Melanoma, Mucosal Melanoma, Mucosal Melanoma of the Head and Neck, Mucosal Melanoma of the Urinary System, Nasopharyngeal Melanoma, Oral Cavity Mucosal Melanoma, Penile Mucosal Melanoma, Rectal Melanoma, Recurrent Mucosal Melanoma, Sinonasal Mucosal Melanoma, Stage II Vulvar Cancer AJCC v8, Stage III Vulvar Cancer AJCC v8, Stage IV Vulvar Cancer AJCC v8, Urethral Melanoma, Vaginal Melanoma, Vulvar Melanoma, Melanoma, Skin, Melanoma/Skin cancer
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
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