Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma

NCT03739372 | Active Not Recruiting DMC

• 2 other identifiers: 170827PNOC008
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 12

Brief Summary

This is a 2 strata pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The study will use a new treatment approach based on each patient's tumor gene expression, whole-exome sequencing (WES), targeted panel profile (UCSF 500 gene panel), and RNA-Seq. The current study will test the efficacy of such an approach in children with High-grade gliomas HGG.

Conditions

Glioma; Glioma of Brain; Cancer; Pediatric Cancer; Pediatric Brain Tumor; Astrocytoma; Glioblastoma; Hemispheric

Keywords

High-grade glioma; whole exome sequencing; WES; genomics; RNA sequencing

Outcome Measures

Primary Outcomes (2)

• 12 month Progression Free Survival (PFS) for Stratum A

  Progression Free Survival will be determined from date of confirmation of response to first evidence of progression or death at the 12 month time point.

  Up to 12 months

• 12 month Overall Survival (OS) for Stratum B

  Overall survival will be determined from the date of histological diagnosis to time of death at the 12 month time point.

  Up to 12 months

Secondary Outcomes (2)

• Frequency of Adverse Events

  From beginning of enrollment up to 30 days post end of treatment.

• Frequency of Serious Adverse Events

  From beginning of enrollment up to 30 days post end of treatment.

Study Arms (2)

Newly diagnosed HGG (Stratum A)

EXPERIMENTAL

Children and young adults with newly diagnosed HGG receive an individualized treatment plan. Each treatment is different and depends on what the Specialized Tumor Board recommends depending on the molecular profile of the patient's tumor.

Other: Specialized tumor board recommendation

Diffuse midline HGG (Stratum B)

EXPERIMENTAL

Children and young adults with diffuse midline high grade gliomas receive an individualized treatment plan. Each treatment is different and depends on what the Specialized Tumor Board recommends depending on the molecular profile of the patient's tumor.

Other: Specialized tumor board recommendation

Interventions

Specialized tumor board recommendation OTHER

Based on the molecular profile, the specialized tumor board will determine an individualized treatment recommendation for each patient using up to four FDA approved drugs. In special circumstances, Investigational new drug (IND) study agents may be used.

Diffuse midline HGG (Stratum B); Newly diagnosed HGG (Stratum A)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with newly diagnosed HGG (including midline HGG but excluding DIPG), who undergo tissue collection as part of standard of care. HGG is defined as either World Health Organization (WHO) grade III or IV, or testing positive for H3K27M mutation. Patients with disseminated disease are not eligible, and MRI of the spine must be performed if disseminated disease is suspected by the treating physician. Primary spinal cord tumors are eligible.
• Enrollment within 3 weeks of the start of radiation therapy.
• Start of radiation therapy within 6 weeks from initial tissue diagnosis.
• Age ≤ 21 years
• Karnofsky score ≥ 50 for patients ≥ 16 years of age and Lansky score ≥ 50 for patients ≤15 years of age. Patients who are unable to walk because of paralysis but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Adequate tissue for molecular profiling (see Section 8 of the protocol for full details)
• The effects of the current treatment paradigm on the developing human fetus are unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception: hormonal or barrier method of birth control; abstinence prior to study entry and for the duration of study participation, and 30 days after completion of study drug administration. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 30 days after completion of study drug administration.
• Adequate neurologic function defined as: Patients with seizure disorder may be enrolled if seizures are well controlled.
• Ability by patient or parent/legal guardian to understand a written informed consent document, and the willingness to sign it.

You may not qualify if:

• Patients who are currently enrolled on another therapeutic clinical trial. Individual cases should be discussed with the study chair.
• Patients who are currently taking any anti-cancer directed therapy. Steroids are not considered anti-cancer therapy. The use of temozolomide during radiation therapy is allowed at standard dosing (maximum 75 to 90 mg/m\^2 daily for a total of 42 days). Any other schedule(s) need to be discussed with the study chair.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).
• Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy. Telemedicine visits are acceptable.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Pacific Pediatric Neuro-Oncology Consortium: collaborator
• The V Foundation for Cancer Research: collaborator

Study Sites (12)

University of California, San Diego Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Children's National Medical Center

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

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Children's Hospitals and Clinics of Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Glioma; Neoplasms; Astrocytoma; Glioblastoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Sabine Mueller, MD, PhD, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: November 13, 2018
• Study Start: November 28, 2018
• Primary Completion: December 31, 2023
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

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

Locations

US (12)