NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening Protocol
概览
- 阶段
- 2 期
- 干预措施
- Mutation Carrier Screening
- 疾病 / 适应症
- Advanced Malignant Solid Neoplasm
- 发起方
- National Cancer Institute (NCI)
- 入组人数
- 1377
- 试验地点
- 291
- 主要终点
- Proportion of Pediatric Patients Whose Advanced Tumors Have Pathway Alterations That Can be Targeted by Select Anti-cancer Drugs
- 状态
- 进行中（未招募）
- 最后更新
- 18天前
概览
简要总结
This phase II Pediatric MATCH screening and multi-sub-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.
详细描述
PRIMARY OBJECTIVES: I. 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. II. To determine the proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs. (Completed as of Amendment #4. Patients enrolled on or after Amendment 4 will not be included in this analysis as screening of unselected patients will no longer be conducted.) SECONDARY OBJECTIVE: I. 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: I. To increase knowledge of the genomic landscape of advanced pediatric solid tumors, non-Hodgkin lymphomas, and histiocytic disorders. II. 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. III. To explore approaches to diagnosing and profiling genomics of advanced pediatric cancers through evaluation of circulating tumor deoxyribonucleic acid (DNA). IV. 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 13 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 erdafitinib PO once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, computed tomography (CT scan), magnetic resonance imaging (MRI), radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study. 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 (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study. 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. APEC1621K: Patients with IDH1 gene mutations receive ivosidenib PO QD. 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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial. After completion of study treatment, patients are followed up periodically.
研究者
入排标准
入选标准
- •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 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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Larotrectinib Sulfate
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Pharmacological Study
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.
干预措施: Vemurafenib
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Pharmacological Study
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.
干预措施: Ulixertinib
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Positron Emission Tomography
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Radionuclide Imaging
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: X-Ray Imaging
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Pharmacological Study
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Pharmacological Study
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Biopsy Procedure
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Aspiration and Biopsy
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Bone Scan
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Computed Tomography
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Laboratory Biomarker Analysis
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Magnetic Resonance Imaging
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Mutation Carrier Screening
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Pharmacological Study
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Pharmacological Study
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Pharmacological Study
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Biopsy Procedure
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Computed Tomography
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Laboratory Biomarker Analysis
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Magnetic Resonance Imaging
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Mutation Carrier Screening
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Pharmacological Study
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Positron Emission Tomography
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.
干预措施: Biopsy Procedure
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Radionuclide Imaging
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: X-Ray Imaging
Subprotocol K (IDH1 gene mutation)
Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Biopsy Procedure
Subprotocol K (IDH1 gene mutation)
Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Biospecimen Collection
Subprotocol K (IDH1 gene mutation)
Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
Subprotocol K (IDH1 gene mutation)
Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Mutation Carrier Screening
Subprotocol 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.
干预措施: Biopsy Procedure
Subprotocol 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.
干预措施: Biospecimen Collection
Subprotocol 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.
干预措施: Laboratory Biomarker Analysis
Subprotocol 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.
干预措施: Mutation Carrier Screening
Subprotocol 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.
干预措施: Pharmacological Study
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.
干预措施: Pharmacological Study
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Aspiration and Biopsy
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Bone Scan
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Computed Tomography
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Pharmacological Study
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Radionuclide Imaging
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: X-Ray Imaging
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Mutation Carrier Screening
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.
干预措施: Pharmacological Study
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.
干预措施: Biopsy Procedure
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.
干预措施: Biospecimen Collection
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.
干预措施: Laboratory Biomarker Analysis
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Biopsy Procedure
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Laboratory Biomarker Analysis
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Magnetic Resonance Imaging
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Mutation Carrier Screening
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Biospecimen Collection
Subprotocol K (IDH1 gene mutation)
Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study
Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Erdafitinib
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.
干预措施: Tazemetostat
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.
干预措施: Samotolisib
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.
干预措施: Selumetinib Sulfate
Subprotocol F (ALK or ROS1 gene alteration)
Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.
干预措施: Ensartinib
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.
干预措施: Olaparib
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.
干预措施: Palbociclib
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. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
干预措施: Selpercatinib
Subprotocol K (IDH1 gene mutation)
Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Ivosidenib
Subprotocol 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.
干预措施: Tipifarnib
结局指标
主要结局
Proportion of Pediatric Patients Whose Advanced Tumors Have Pathway Alterations That Can be Targeted by Select Anti-cancer Drugs
时间窗: Up to 2 years from study entry
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. Patients enrolled on or after Amendment 4 will not be included in this analysis as screening of unselected patients will no longer be conducted.
Proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs
时间窗: Up to 2 years from study entry
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. Patients enrolled on or after Amendment 4 will not be included in this analysis as screening of unselected patients will no longer be conducted.
次要结局
- Objective Response Rate (ORR) to Targeted Therapy in Tumors Lacking Actionable Alterations(Up to 2 years from study entry)
- Objective response rate (ORR) to targeted therapy in tumors lacking actionable alterations(Up to 2 years from study entry)