Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma
Start Date
2/22/2022
Completion Date
1/31/2028
Summary
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 in the pilot phase of performing real-time drug screening on tissue taken during surgery in patients with relapsed medulloblastoma or ependymoma 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 relapsed medulloblastoma and ependymoma 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. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.
Detailed Description
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.
Eligibility Criteria
Age Range: No minimum to 39 years
Interventions
Specialized Tumor Board Treatment Plan
Combinations
Conditions
Locations
Children's Hospital of Los Angeles
Los Angeles, California 90027
United States
Rady Children's Hospital
San Diego, California 92123
United States
University of California, San Francisco
San Francisco, California 94143
United States
Children's National Hospital
Washington D.C., District of Columbia 20010
United States
St. Louis Children's Hospital / Washington University in St. Louis
St Louis, Missouri 63130
United States
New York University
New York, New York 10016
United States
Columbia University Medical Center
New York, New York 10032
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States