This is a single arm multi-center pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). Relapsed participants will receive an individualized treatment recommendation including up to four FDA-approved drugs based on the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.~PRIMARY OBJECTIVE:~I. To determine the feasibility of using the results of real-time in vitro drug screening, whole exome sequencing, and RNA sequencing of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma.~SECONDARY OBJECTIVE:~I. To determine the safety and describe the toxicity of treating children and young adults with relapsed medulloblastoma according to a specialized tumor board that makes treatment recommendations based on real-time drug screening and genomic sequencing.~EXPLORATORY OBJECTIVES:~I. To estimate the objective response rate, progression free survival at 6 months (PFS-6) and overall survival (OS) of relapsed medulloblastoma in children and young adults treated with an individualized treatment regimen.~II. To assess Quality of Life (QOL) measures in participants with relapsed medulloblastoma treated with an individualized regimen.~III. To archive tumor and normal DNA from each participant along with serial blood draw following therapies as biospecimens for later studies to determine whether circulating tumor DNA (ctDNA) sequences in the participant's blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance.~Participants may continue treatment as tolerated for up to two years or until disease progression. Participants will be followed until progression, death, or up to 5 years from start of therapy.
The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility of performing real-time drug screening on tissue taken during surgery, and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with medulloblastoma to receive the most effective and least toxic therapies currently available, and will pave the way for improved understanding and treatment of these tumors in the future.