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Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Study details:
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) 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:. I.
To estimate the progression free survival in pediatric patients receiving targeted therapies for advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders. II. To obtain preliminary or additional information about the tolerability of targeted therapies in children with advanced cancers.
III. To provide preliminary estimates of the pharmacokinetics of targeted therapies in children with advanced cancers. IV.
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 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 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. 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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 12 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2017-07-31
Primary completion: 2025-03-31
Study completion finish: 2026-05-09
Study type
SCREENING
Phase
PHASE2
Trial ID
NCT03155620
Intervention or treatment
PROCEDURE: Biopsy
PROCEDURE: Biospecimen Collection
PROCEDURE: Bone Marrow Aspiration and Biopsy
PROCEDURE: Bone Scan
PROCEDURE: Computed Tomography
DRUG: Ensartinib
DRUG: Erdafitinib
OTHER: Laboratory Biomarker Analysis
DRUG: Larotrectinib Sulfate
PROCEDURE: Magnetic Resonance Imaging
PROCEDURE: Mutation Carrier Screening
DRUG: Olaparib
DRUG: Palbociclib
OTHER: Pharmacological Study
PROCEDURE: Positron Emission Tomography
PROCEDURE: Radionuclide Imaging
DRUG: Samotolisib
DRUG: Selpercatinib
DRUG: Selumetinib Sulfate
DRUG: Tazemetostat
DRUG: Tipifarnib
DRUG: Ulixertinib
DRUG: Vemurafenib
PROCEDURE: X-Ray Imaging
Conditions
- • Advanced Malignant Solid Neoplasm
- • Ann Arbor Stage III Non-Hodgkin Lymphoma
- • Ann Arbor Stage IV Non-Hodgkin Lymphoma
- • Histiocytic Sarcoma
- • Juvenile Xanthogranuloma
- • Langerhans Cell Histiocytosis
- • Malignant Glioma
- • Recurrent Childhood Rhabdomyosarcoma
- • Recurrent Ependymoma
- • Recurrent Ewing Sarcoma
- • Recurrent Glioma
- • Recurrent Hepatoblastoma
- • Recurrent Langerhans Cell Histiocytosis
- • Recurrent Malignant Germ Cell Tumor
- • Recurrent Malignant Solid Neoplasm
- • Recurrent Medulloblastoma
- • Recurrent Neuroblastoma
- • Recurrent Non-Hodgkin Lymphoma
- • Recurrent Osteosarcoma
- • Recurrent Peripheral Primitive Neuroectodermal Tumor
- • Recurrent Primary Central Nervous System Neoplasm
- • Recurrent Rhabdoid Tumor
- • Recurrent Soft Tissue Sarcoma
- • Refractory Ewing Sarcoma
- • Refractory Glioma
- • Refractory Hepatoblastoma
- • Refractory Langerhans Cell Histiocytosis
- • Refractory Malignant Germ Cell Tumor
- • Refractory Malignant Solid Neoplasm
- • Refractory Medulloblastoma
- • Refractory Neuroblastoma
- • Refractory Non-Hodgkin Lymphoma
- • Refractory Osteosarcoma
- • Refractory Peripheral Primitive Neuroectodermal Tumor
- • Refractory Primary Central Nervous System Neoplasm
- • Refractory Rhabdoid Tumor
- • Refractory Rhabdomyosarcoma
- • Rhabdoid Tumor
- • Stage III Osteosarcoma AJCC v7
- • Stage III Soft Tissue Sarcoma AJCC v7
- • Stage IV Osteosarcoma AJCC v7
- • Stage IV Soft Tissue Sarcoma AJCC v7
- • Stage IVA Osteosarcoma AJCC v7
- • Stage IVB Osteosarcoma AJCC v7
- • Wilms Tumor
Find a site
Closest Location:
Perth Children's Hospital
Research sites nearby
Select from list below to view details:
Perth Children's Hospital
Perth, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Subprotcol M (HRAS gene alterations)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol C (EZH2, SMARCB1, or SMARCA4 gene mutation)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol D (TSC1, TSC2, or PI3K/mTOR gene mutation)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol E (activating MAPK pathway gene mutation)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol F (ALK or ROS1 gene alteration)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol G (BRAF V600 gene mutation)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol H (ATM, BRCA1, BRCA2, RAD51C, RAD51D mutations)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol I (Rb positive, alterations in cell cycle genes)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol J (MAPK pathway mutations)
| PROCEDURE: Biopsy
|
EXPERIMENTAL: Subprotocol N (activating RET mutations)
| PROCEDURE: Biopsy
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Objective response rate (complete response/partial response) | 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. | From enrollment to the end of treatment, up to 2 years on subprotocol |
Proportion of pediatric patients whose advanced tumors have pathway alterations that can be targeted by select anti-cancer drugs | 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. | Up to 4 years |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Percentage of patients with grade 3 or 4 adverse events | 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. | From enrollment to the end of treatment, up to 2 years on subprotocol |
Incidence of research biopsy related target toxicity | 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. | Up to 14 days |
Progression free survival (PFS) | Will be estimated using the Kaplan-Meier method along with confidence intervals. | 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 |
Pharmacokinetic (PK) parameters | A descriptive analysis of PK parameters will be performed in specific subprotocols to define systemic exposure, drug clearance, and other pharmacokinetic parameters. | Up to 4 years |
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