Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma

This is a 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: For pilot phase (CLOSED TO ENROLLMENT): 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 or ependymoma For efficacy phase: II. To determine the progression-free survival (PFS) in children and young adults with relapsed medulloblastoma and ependymoma who received the specialized tumor board recommendation and compare to historical cohorts. SECONDARY OBJECTIVE: For pilot (CLOSED TO ENROLLMENT) and efficacy phases: I. To determine the safety and describe the toxicity of treating children and young adults with relapsed medulloblastoma and ependymoma according to a specialized tumor board recommended treatment plan. EXPLORATORY OBJECTIVES: Pilot Phase (CLOSED TO ENROLLMENT): 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 cfDNA sequences in the participant's blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance. Efficacy Phase: I. To determine the overall survival (OS) and objective response rate (ORR) in children and young adults with relapsed medulloblastoma and ependymoma who received the specialized tumor board recommendation and compare to historical cohorts. II. To generate PDX models of relapsed medulloblastoma and ependymoma to facilitate future in vivo testing of therapeutic agents. III. To assess the correlation between available genomic data (WES and RNAseq) and patient outcomes, evaluating its potential complementary role in guiding therapeutic decisions alongside the primary drug screening approach. IV. To archive tumor and normal DNA from each participant along with serial blood draw following therapies as biospecimens for later studies to determine whether cell free DNA (cfDNA) sequences in the participant's blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance. V. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks. VI. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks. Participants were initially enrolled in a pilot phase (CLOSED TO ENROLLMENT), and additional participants will be enrolled in the efficacy phase. Participants may continue treatment as tolerated for up to two years or until disease progression. After two years, patients may be eligible to continue therapy if they are experiencing clinical benefits, have disease control, and it is deemed appropriate to do so by their physician. Participants will be followed until progression, death, or up to 5 years from start of therapy.