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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
74
Specialized Treatment Plan of up to four FDA approved drugs based on participant's screening results will be assigned by PNOC specialized tumor board
Specialized Treatment Plan of up to four FDA approved drugs based on participant's screening results will be assigned by PNOC specialized tumor board
Children's Hospital of Los Angeles
Los Angeles, California, United States
RECRUITINGRady Children's Hospital
San Diego, California, United States
RECRUITINGUniversity of California, San Francisco
San Francisco, California, United States
RECRUITINGChildren's National Hospital
Washington D.C., District of Columbia, United States
RECRUITINGSt. Louis Children's Hospital / Washington University in St. Louis
St Louis, Missouri, United States
RECRUITINGNew York University
New York, New York, United States
RECRUITINGColumbia University Medical Center
New York, New York, United States
RECRUITINGChildren's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
RECRUITINGNumber of participants for whom treatment recommendations are fully completed within 21 business days of tissue collection based on drug screening (Pilot Phase)
Time to tissue collection will be used to determine the feasibility of using the results of real-time in vitro drug screening, WES and RNAseq 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. Participants are expected to receive treatment plan within 21 business days
Time frame: Up to 21 days
Percentage of participants with treatment recommendations within 21 business days (Pilot Phase)
Time to tissue collection will be used to determine the feasibility of using the results of real-time in vitro drug screening, WES and RNAseq 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. Participants are expected to receive treatment plan within 21 business days
Time frame: Up to 21 days
Number of participants without adequate tissue
The number of consented participants who do not have adequate tissue collection will be used to determine the feasibility.
Time frame: Up to 21 days
Median Time from tissue collection to issued treatment plan from the specialized tumor board (Pilot Phase)
Time to tissue collection will be used to determine the feasibility of using the results of real-time in vitro drug screening, WES and RNAseq 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. Participants are expected to receive treatment plan within 21 business days
Time frame: Up to 21 days
Median Progression-free survival (PFS) (Efficacy Phase)
The median months from the time of surgery for this recurrence to the first evidence of progression or death, using PFS at 10 months (PFS10) for the relapsed medulloblastoma cohort and PFS at 17 months for the relapsed ependymoma cohort (Arm B).
Time frame: Up to 5 years
Proportion of participants with Adverse Events
Proportion of participants with grade 3 or higher toxicities classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3 or higher criteria will be summarized by maximum grade and relationship to study drug(s).
Time frame: Up to 2 years
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