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

NCT05057702 | Recruiting DMC

• 2 other identifiers: 21083NCI-2021-09726
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Medulloblastoma; Medulloblastoma, Childhood; Medulloblastoma Recurrent; Ependymoma; Ependymoma Malignant; Ependymoma of Brain

Keywords

Individualized Treatment Plan; Genetic Screening; Screening

Outcome Measures

Primary Outcomes (5)

• Number 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

  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

  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.

  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

  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).

  Up to 5 years

Secondary Outcomes (1)

• Proportion of participants with Adverse Events

  Up to 2 years

Study Arms (2)

Individualized Treatment Recommendation (Pilot Phase)

EXPERIMENTAL

Participants will receive an individualized treatment recommendation including a combination of up to four FDA-approved drugs within 21 business days of tissue acquisition using the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

Other: Specialized Tumor Board Treatment Plan; Other: Combinations

Individualized Treatment Recommendation (Efficacy Phase)

EXPERIMENTAL

Participants will receive an individualized treatment recommendation including a combination of up to four FDA-approved drugs within 21 business days of tissue acquisition using the results of real-time high-throughput drug screening, whole exome sequencing (WES), and RNA sequencing.

Other: Specialized Tumor Board Treatment Plan; Other: Combinations

Interventions

Specialized Tumor Board Treatment Plan OTHER

Specialized Treatment Plan of up to four FDA approved drugs based on participant's screening results will be assigned by PNOC specialized tumor board

Also known as: Individualized Treatment Plan, Specialized Treatment Plan

Individualized Treatment Recommendation (Efficacy Phase); Individualized Treatment Recommendation (Pilot Phase)

Combinations OTHER

Specialized Treatment Plan of up to four FDA approved drugs based on participant's screening results will be assigned by PNOC specialized tumor board

Also known as: Multiple Treatments Physician Discretion

Individualized Treatment Recommendation (Efficacy Phase); Individualized Treatment Recommendation (Pilot Phase)

Eligibility Criteria

• Age: 12 Months - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible.
• Participants must have surgically accessible disease.
• Prior Therapy:
• The participant must have received at least one prior therapy at the time of initial diagnosis.
• Relapsed medulloblastoma or relapsed ependymoma are eligible.
• Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines
• Participants must have received last chemotherapy or biologic agent at least 7 days prior to registration.
• Monoclonal antibody treatment: \> 21 days prior to registration.
• Bevacizumab participants must have received last dose \> 21 days prior to study registration
• Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study.
• Radiation - Participants must have:
• Had their last fraction of local irradiation to primary tumor \>= 12 weeks prior to registration.
• Had their last fraction of craniospinal irradiation or total body irradiation \>= 12 weeks prior to registration
• At least 14 days after local palliative radiation (small-port)
• Age \>=12 months to \<= 39 years of age.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants who are receiving any other investigational agents.
• Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
• Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
• Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.
• Participants must not receive any tumor-directed therapy after enrollment, except for surgical resection/ biopsy.
• Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.

Sponsors & Collaborators

• University of California, San Francisco: lead
• St. Baldrick's Foundation: collaborator
• Ashion Analytics: collaborator
• University of Washington: collaborator
• Pediatric Neuro-Oncology Consortium: collaborator
• Washington University School of Medicine: collaborator

Study Sites (8)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

St. Louis Children's Hospital / Washington University in St. Louis

St Louis, Missouri, 63130, United States

RECRUITING

New York University

New York, New York, 10016, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Medulloblastoma; Ependymoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Sabine Mueller, MD, PhD, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Robert Wechsler-Reya, PhD

  Columbia University

  STUDY CHAIR

• Margaret Shatara, MD

  Children's Minnesota

  STUDY CHAIR

• Megan Paul, MD

  Rady Children's Hospital

  STUDY CHAIR

• Lindsay Kilburn, MD

  Children's National Research Institute

  STUDY CHAIR

Central Study Contacts

PNOC Operation Office

CONTACT

415-502-1600; PNOC027@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2021
• First Posted: September 27, 2021
• Study Start: February 22, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (8)