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)
Study Details
Study Description
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES:
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To utilize clinical and biological data to screen for eligibility to phase 2 pathway-targeting specific subprotocols of pathway-targeting agents in pediatric patients with advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
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To determine the proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs. (Completed) III. To determine the objective response rates (ORR; complete response + partial response) in pediatric patients with advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders harboring a priori specified genomic alterations treated with pathway-targeting agents.
SECONDARY OBJECTIVES:
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To estimate the progression free survival in pediatric patients receiving targeted therapies for advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
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To obtain preliminary or additional information about the tolerability of targeted therapies in children with advanced cancers.
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To provide preliminary estimates of the pharmacokinetics of targeted therapies in children with advanced cancers.
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To obtain preliminary information on the response rate to targeted therapy in patients whose tumors lack actionable alterations as defined for the molecular analysis for therapy choice (MATCH) study, for selected agents for which efficacy is observed in the primary matched cohort.
EXPLORATORY OBJECTIVES:
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To increase knowledge of the genomic landscape of advanced pediatric solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
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To describe the genomic changes that occur in advanced pediatric cancers between the time of initial diagnosis and relapse, in cases for which paired tumor specimens are available.
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To explore approaches to diagnosing and profiling genomics of advanced pediatric cancers through evaluation of circulating tumor deoxyribonucleic acid (DNA).
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To determine the frequency and spectrum of germline cancer susceptibility mutations in children with relapsed solid tumors and non-Hodgkin lymphomas and assess the feasibility of return of those results in the National Clinical Trial Network (NCTN) group setting.
OUTLINE:
STEP 1 (SCREENING): Patients undergo biopsy along with tumor mutational screening of the biopsy material for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing and immunohistochemistry. Patients also undergo collection of blood samples for research purposes.
STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational drugs used in this study or those without mutations are assigned to 1 of 10 treatment subprotocols.
APEC1621A: Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib sulfate orally (PO) or via nasogastric- or gastric-tube twice daily (BID) on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621B: Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive pan-FGFR tyrosine kinase inhibitor JNJ-42756493 PO once daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621C: Patients with an EZH2, SMARCB1, or SMARCA4 gene mutation receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621D: Patients with a TSC1, TSC2, or PI3K/mTOR gene mutations receive PI3K/mTOR inhibitor LY3023414 PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621E: Patients with an activating MAPK pathway gene mutation receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621F: Patients with an ALK or ROS1 gene alteration receive ensartinib (ALK Inhibitor X-396) PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621G: Patients with a BRAF V600 gene mutation receive vemurafenib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621H: Patients with deleterious ATM, BRCA1, BRCA2, RAD51C, or RAD51D gene mutations receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621I: Patients with Rb positive advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations in cell cycle genes receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621J: Patients with MAPK Pathway Mutations receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621M: Patients with HRAS gene alterations receive tipifarnib PO or via nasogastric or gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
APEC1621N: Patients with activating RET gene alterations receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Subprotcol M (HRAS gene alterations) Patients receive tipifarnib PO or via nasogastric or gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Tipifarnib
Given PO or via nasogastric or gastric tube
Other Names:
|
| Experimental: Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion) Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib sulfate PO or via nasogastric- or gastric-tube BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Drug: Larotrectinib Sulfate
Given PO or via nasogastric- or gastric-tube
Other Names:
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
|
| Experimental: Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation) Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive pan-FGFR tyrosine kinase inhibitor JNJ-42756493 PO once daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Drug: Erdafitinib
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
|
| Experimental: Subprotocol C (EZH2, SMARCB1, or SMARCA4 gene mutation) Patients with an EZH2, SMARCB1, or SMARCA4 gene mutation receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Tazemetostat
Given PO
Other Names:
|
| Experimental: Subprotocol D (TSC1, TSC2, or PI3K/mTOR gene mutation) Patients with a TSC1, TSC2, or PI3K/mTOR gene mutations receive PI3K/mTOR inhibitor LY3023414 PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Samotolisib
Given PO
Other Names:
|
| Experimental: Subprotocol E (activating MAPK pathway gene mutation) Patients with an activating MAPK pathway gene mutation receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Selumetinib Sulfate
Given PO
Other Names:
|
| Experimental: Subprotocol F (ALK or ROS1 gene alteration) Patients with an ALK or ROS1 gene alteration receive ensartinib (ALK Inhibitor X-396) PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Drug: Ensartinib
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
|
| Experimental: Subprotocol G (BRAF V600 gene mutation) Patients with a BRAF V600 gene mutation receive vemurafenib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Vemurafenib
Given PO
Other Names:
|
| Experimental: Subprotocol H (ATM, BRCA1, BRCA2, RAD51C, RAD51D mutations) Patients deleterious ATM, BRCA1, BRCA2, RAD51C, or RAD51D gene mutations receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Drug: Olaparib
Given PO
Other Names:
Other: Pharmacological Study
Correlative studies
|
| Experimental: Subprotocol I (Rb positive, alterations in cell cycle genes) Patients with Rb positive advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations in cell cycle genes receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Drug: Palbociclib
Given PO
Other Names:
Other: Pharmacological Study
Correlative studies
|
| Experimental: Subprotocol J (MAPK pathway mutations) Patients with MAPK pathway mutations receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Ulixertinib
Receive PO
Other Names:
|
| Experimental: Subprotocol N (activating RET mutations) Patients with activating RET gene alterations receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
Other: Laboratory Biomarker Analysis
Undergo molecular analysis
Procedure: Mutation Carrier Screening
Undergo tumor tissue mutation screening
Other: Pharmacological Study
Correlative studies
Drug: Selpercatinib
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective response rate (complete response/partial response) [From enrollment to the end of treatment, up to 2 years on subprotocol]
Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.
- Proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs [Up to 4 years]
Match rate will be calculated as the percent of eligible patients who have an actionable mutation of interest and are matched to at least one of the subprotocols, and confidence intervals will be constructed using the Wilson score interval method.
Secondary Outcome Measures
- Percentage of patients with grade 3 or 4 adverse events [From enrollment to the end of treatment, up to 2 years on subprotocol]
Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.
- Incidence of research biopsy related target toxicity [Up to 14 days]
Defined as any >= grade 3 toxicity or complication that is probably or definitely attributable to any biopsy-related anesthesia or imaging procedures that occurs within 14 days of research.
- Progression free survival (PFS) [From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 4 years]
Will be estimated using the Kaplan-Meier method along with confidence intervals.
- Pharmacokinetic (PK) parameters [Up to 4 years]
A descriptive analysis of PK parameters will be performed in specific subprotocols to define systemic exposure, drug clearance, and other pharmacokinetic parameters.
Other Outcome Measures
- Genomic landscape of advanced pediatric solid tumors, non-Hodgkin lymphomas, and histiocytic disorders [Up to 4 years]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
- Change in genomics in advanced pediatric cancers [Baseline up to 4 years]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
- Diagnostic and profiling genomics of tumor approach [Up to 4 years]
Will be evaluated through circulating tumor deoxyribonucleic acid (DNA). A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature.
- Frequency of germline cancer susceptibility mutations in children with relapsed solid tumors and non-Hodgkin lymphomas [Up to 4 years]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature. Will assess the feasibility of return of the results in the National Clinical Trial Network (NCTN) group setting.
- Spectrum of germline cancer susceptibility mutations in children with relapsed solid tumors and non-Hodgkin lymphomas [Up to 4 years]
A descriptive analysis will be performed and will be summarized with simple summary statistics. This analysis will be descriptive in nature. Will assess the feasibility of return of the results in the NCTN group setting.
Eligibility Criteria
Criteria
Inclusion Criteria:
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ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
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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
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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
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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
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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
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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
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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)
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Note: The following do not qualify as measurable disease:
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Malignant fluid collections (e.g., ascites, pleural effusions)
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Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
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Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
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Elevated tumor markers in plasma or CSF
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Previously radiated lesions that have not demonstrated clear progression post radiation
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Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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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
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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
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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
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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
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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)
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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
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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
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Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
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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
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Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
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Stem cell infusions (with or without total-body irradiation [TBI]):
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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)
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Autologous stem cell infusion including boost infusion: >= 42 days
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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.)
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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
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Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
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GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
-
Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
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Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
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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
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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
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Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
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Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
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Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
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Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
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GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
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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)
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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
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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
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GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
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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
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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
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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
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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
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GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
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GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
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GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
| 2 | Providence Alaska Medical Center | Anchorage | Alaska | United States | 99508 |
| 3 | Banner Children's at Desert | Mesa | Arizona | United States | 85202 |
| 4 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
| 5 | Banner University Medical Center - Tucson | Tucson | Arizona | United States | 85719 |
| 6 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
| 7 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
| 8 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 9 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 10 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
| 11 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 12 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 13 | Mattel Children's Hospital UCLA | Los Angeles | California | United States | 90095 |
| 14 | Valley Children's Hospital | Madera | California | United States | 93636 |
| 15 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 16 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 17 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 18 | Lucile Packard Children's Hospital Stanford University | Palo Alto | California | United States | 94304 |
| 19 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 20 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
| 21 | Naval Medical Center -San Diego | San Diego | California | United States | 92134 |
| 22 | UCSF Medical Center-Mission Bay | San Francisco | California | United States | 94158 |
| 23 | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California | United States | 90502 |
| 24 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 25 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
| 26 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
| 27 | Yale University | New Haven | Connecticut | United States | 06520 |
| 28 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
| 29 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
| 30 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 31 | Broward Health Medical Center | Fort Lauderdale | Florida | United States | 33316 |
| 32 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
| 33 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
| 34 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
| 35 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
| 36 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 37 | Nicklaus Children's Hospital | Miami | Florida | United States | 33155 |
| 38 | AdventHealth Orlando | Orlando | Florida | United States | 32803 |
| 39 | Arnold Palmer Hospital for Children | Orlando | Florida | United States | 32806 |
| 40 | Nemours Children's Hospital | Orlando | Florida | United States | 32827 |
| 41 | Nemours Children's Clinic - Pensacola | Pensacola | Florida | United States | 32504 |
| 42 | Sacred Heart Hospital | Pensacola | Florida | United States | 32504 |
| 43 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
| 44 | Tampa General Hospital | Tampa | Florida | United States | 33606 |
| 45 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
| 46 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
| 47 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
| 48 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
| 49 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
| 50 | Saint Luke's Cancer Institute - Boise | Boise | Idaho | United States | 83712 |
| 51 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
| 52 | University of Illinois | Chicago | Illinois | United States | 60612 |
| 53 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
| 54 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 55 | Saint Jude Midwest Affiliate | Peoria | Illinois | United States | 61637 |
| 56 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 57 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 58 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
| 59 | Blank Children's Hospital | Des Moines | Iowa | United States | 50309 |
| 60 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
| 61 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 62 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 63 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
| 64 | Ochsner Medical Center Jefferson | New Orleans | Louisiana | United States | 70121 |
| 65 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 66 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
| 67 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 68 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 69 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 70 | National Institutes of Health Clinical Center | Bethesda | Maryland | United States | 20892 |
| 71 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 72 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 73 | UMass Memorial Medical Center - University Campus | Worcester | Massachusetts | United States | 01655 |
| 74 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 75 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 76 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
| 77 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
| 78 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 79 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
| 80 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 81 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 82 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 83 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
| 84 | Cardinal Glennon Children's Medical Center | Saint Louis | Missouri | United States | 63104 |
| 85 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 86 | Mercy Hospital Saint Louis | Saint Louis | Missouri | United States | 63141 |
| 87 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
| 88 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 89 | University Medical Center of Southern Nevada | Las Vegas | Nevada | United States | 89102 |
| 90 | Sunrise Hospital and Medical Center | Las Vegas | Nevada | United States | 89109 |
| 91 | Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | United States | 89135 |
| 92 | Summerlin Hospital Medical Center | Las Vegas | Nevada | United States | 89144 |
| 93 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 94 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 95 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
| 96 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
| 97 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
| 98 | Albany Medical Center | Albany | New York | United States | 12208 |
| 99 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 100 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
| 101 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
| 102 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
| 103 | NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York | United States | 10032 |
| 104 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 105 | NYP/Weill Cornell Medical Center | New York | New York | United States | 10065 |
| 106 | University of Rochester | Rochester | New York | United States | 14642 |
| 107 | Stony Brook University Medical Center | Stony Brook | New York | United States | 11794 |
| 108 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
| 109 | New York Medical College | Valhalla | New York | United States | 10595 |
| 110 | Mission Hospital | Asheville | North Carolina | United States | 28801 |
| 111 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 112 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
| 113 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
| 114 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 115 | East Carolina University | Greenville | North Carolina | United States | 27834 |
| 116 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 117 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
| 118 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 119 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
| 120 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 121 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 122 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
| 123 | ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Toledo | Ohio | United States | 43606 |
| 124 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 125 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
| 126 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 127 | Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | United States | 18103 |
| 128 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 129 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 130 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
| 131 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 132 | Prisma Health Richland Hospital | Columbia | South Carolina | United States | 29203 |
| 133 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
| 134 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
| 135 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
| 136 | Saint Jude Children's Research Hospital | Memphis | Tennessee | United States | 38105 |
| 137 | The Children's Hospital at TriStar Centennial | Nashville | Tennessee | United States | 37203 |
| 138 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 139 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
| 140 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
| 141 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 142 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
| 143 | El Paso Children's Hospital | El Paso | Texas | United States | 79905 |
| 144 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 145 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
| 146 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 147 | Covenant Children's Hospital | Lubbock | Texas | United States | 79410 |
| 148 | UMC Cancer Center / UMC Health System | Lubbock | Texas | United States | 79415 |
| 149 | Children's Hospital of San Antonio | San Antonio | Texas | United States | 78207 |
| 150 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
| 151 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
| 152 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 153 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
| 154 | University of Vermont and State Agricultural College | Burlington | Vermont | United States | 05405 |
| 155 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
| 156 | Naval Medical Center - Portsmouth | Portsmouth | Virginia | United States | 23708-2197 |
| 157 | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | United States | 23298 |
| 158 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 159 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
| 160 | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | United States | 98405 |
| 161 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431 |
| 162 | West Virginia University Healthcare | Morgantown | West Virginia | United States | 26506 |
| 163 | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | United States | 53792 |
| 164 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 165 | San Jorge Children's Hospital | San Juan | Puerto Rico | 00912 | |
| 166 | University Pediatric Hospital | San Juan | Puerto Rico | 00926 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Donald W Parsons, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2017-01251
- NCI-2017-01251
- APEC1621SC
- APEC1621SC
- U10CA180886