Pediatric MATCH

Pediatric MATCH
Title	Pediatric MATCH
Abbreviation	Pediatric MATCH
Sponsor	National Cancer Institute
Location	United States
Phase	Umbrella/basket
Condition	Pediatric solid tumors and hematologic malignancies
Interventions	Targeted therapies based on molecular alterations

Pediatric MATCH Pediatric MATCH is a precision oncology clinical trial for children and adolescents with refractory or recurrent solid tumors and hematologic malignancies who have exhausted standard therapies. It matches participants to targeted agents based on genomic alterations identified through centralized molecular profiling. The study is coordinated by the National Cancer Institute and conducted across multiple pediatric oncology centers and cooperative groups.

Overview

Pediatric MATCH was launched to adapt the framework of adult precision oncology initiatives to pediatric malignancies, drawing on precedents such as NCI-MATCH, The Cancer Genome Atlas, St. Jude Children’s Research Hospital genomic efforts, Dana-Farber Cancer Institute collaborations, and international consortia including European Society for Paediatric Oncology projects. The trial integrates diagnostics from clinical laboratories like Foundation Medicine, academic sequencing centers such as Broad Institute, and pediatric cooperative groups including Children's Oncology Group and Pediatric Oncology Group. Designed as an umbrella and basket study, it leverages partnerships with pharmaceutical companies including Novartis, Pfizer, Merck & Co., AstraZeneca, and Seagen to provide investigational and approved agents.

Trial Design and Methods

The study employs a molecularly guided allocation algorithm modeled after trials such as BATTLE and I-SPY, utilizing next-generation sequencing platforms and orthogonal assays. Central review panels composed of molecular pathologists from institutions like Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Boston Children's Hospital adjudicate actionable alterations and assign therapy. The protocol features multiple single-arm treatment cohorts (baskets) defined by biomarkers, with Simon two-stage designs and adaptive enrollment strategies influenced by methodology from Adaptive clinical trial literature and statistical approaches espoused by groups at Fred Hutchinson Cancer Center and MD Anderson Cancer Center.

Eligibility and Enrollment

Eligibility criteria mirror those of pediatric oncology trials run by groups such as Children's Hospital of Philadelphia and require recurrent or refractory disease following standard management protocols exemplified by guidelines from American Society of Clinical Oncology and pediatric committees at European Medicines Agency. Enrollment pathways include referrals from tertiary centers like Riley Hospital for Children, regional pediatric oncology units, and international collaborators. Informed consent and assent procedures reference regulatory frameworks from Food and Drug Administration guidances and institutional review boards at universities such as University of California, San Francisco and Yale School of Medicine.

Molecular Testing and Biomarkers

Centralized molecular profiling uses panels akin to assays developed at Broad Institute and commercial tests from Foundation Medicine and Guardant Health, supplemented by immunohistochemistry and fluorescence in situ hybridization methods pioneered at Mayo Clinic and Cleveland Clinic. Targetable alterations frequently assessed include mutations, amplifications, and fusions found in genes studied at institutions like Cold Spring Harbor Laboratory and Wellcome Sanger Institute, with biomarkers such as alterations in BRAF, ALK, NTRK, mTOR pathway components, and PIK3CA drawing on literature from American Association for Cancer Research conferences. Bioinformatics pipelines incorporate tools developed by groups at European Bioinformatics Institute and Carnegie Mellon University to call variants and annotate clinical actionability.

Treatment Arms and Drugs

Treatment arms include targeted agents supported by pharmaceutical partners such as Novartis (e.g., BRAF/MEK inhibitors), Pfizer (ALK inhibitors), Loxo Oncology/Eli Lilly (TRK inhibitors), AstraZeneca (PI3K/mTOR pathway agents), and antibody-drug conjugates from Seagen. Arms are structured to test drugs in biomarker-defined cohorts similar to strategies used in trials like NCI-MATCH and pediatric substudies at St. Jude Children’s Research Hospital. Dose selection and pediatric formulation considerations reference pediatric pharmacology expertise from University of Michigan and regulatory pediatric investigation plans filed with European Medicines Agency.

Results and Impact

Published results from Pediatric MATCH cohorts have been reported at meetings of American Society of Clinical Oncology and in journals associated with Journal of Clinical Oncology and The Lancet Oncology, demonstrating both successes and limitations of genomically matched therapy in pediatric populations. Outcomes include objective responses in subsets with alterations such as NTRK fusions and resistant disease in cohorts with complex karyotypes, informing subsequent studies at centers like St. Jude Children’s Research Hospital and influencing trial design at cooperative groups including Children's Oncology Group. The trial has impacted precision medicine policy discussions at agencies like the National Institutes of Health and stimulated translational research collaborations with institutes such as Institute of Cancer Research.

Ethical and Regulatory Considerations

Ethical issues addressed by the protocol reflect debates in pediatric research ethics discussed at forums hosted by UNICEF and World Health Organization, including consent/assent, return of incidental findings, and equity of access. Regulatory oversight involves interactions with Food and Drug Administration for investigational new drug approvals and safety reporting, institutional review boards at academic centers like Columbia University Irving Medical Center, and data-sharing policies aligned with initiatives from Global Alliance for Genomics and Health. The trial's experience has informed guidance on pediatric molecular testing reimbursement and compassionate use policies advocated by patient advocacy groups such as St. Baldrick's Foundation and Alex's Lemonade Stand Foundation.

Category:Clinical trials Category:Pediatric oncology