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Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma (PNOC008)

Primary Purpose

Glioma, Glioma of Brain, Cancer

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Specialized tumor board recommendation
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioma focused on measuring High-grade glioma, whole exome sequencing, WES, genomics, RNA sequencing

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • University of California, San Diego Rady Children's Hospital
  • University of California, San Francisco
  • Children's National Medical Center
  • University of Florida
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Johns Hopkins University
  • Children's Hospitals and Clinics of Minneapolis
  • Washington University
  • Nationwide Children's Hospital
  • The Children's Hospital Of Philadelphia
  • University of Utah
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Newly diagnosed HGG (Stratum A)

Diffuse midline HGG (Stratum B)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Frequency of Adverse Events
Toxicity will be described by reporting Adverse Events (AE). Events will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. All study-related and unrelated AEs will be collected and reported, together with their maximum intensity among all recorded respective AE.
Frequency of Serious Adverse Events
Toxicity will be described by reporting Serious Adverse Events (SAE). Events will be assessed according to the NCI CTCAE v5.0. All study-related and unrelated Serious Adverse Events (SAE) will be collected and reported, together with their maximum intensity among all recorded respective SAE.

Full Information

First Posted
November 2, 2018
Last Updated
February 23, 2023
Sponsor
University of California, San Francisco
Collaborators
Pacific Pediatric Neuro-Oncology Consortium, The V Foundation for Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT03739372
Brief Title
Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma
Acronym
PNOC008
Official Title
A Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children and Young Adults With High Grade Glioma (Excluding Diffuse Intrinsic Pontine Glioma)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 28, 2018 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Pacific Pediatric Neuro-Oncology Consortium, The V Foundation for Cancer Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
For children with High-grade gliomas (HGG) including HGG presenting within the midline structures of the brain and spine, outcome remains poor and the majority of children die from this disease. The current 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. This treatment strategy has shown promising results in adult patients with solid tumors and is currently being explored in children with DIPG, neuroblastoma and other solid tumors. The current study will test the efficacy of such an approach in children with HGG for which outcomes remain dismal.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma, Glioma of Brain, Cancer, Pediatric Cancer, Pediatric Brain Tumor, Astrocytoma, Glioblastoma, Hemispheric
Keywords
High-grade glioma, whole exome sequencing, WES, genomics, RNA sequencing

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Newly diagnosed HGG (Stratum A)
Arm Type
Experimental
Arm Description
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.
Arm Title
Diffuse midline HGG (Stratum B)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Specialized tumor board recommendation
Intervention Description
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.
Primary Outcome Measure Information:
Title
12 month Progression Free Survival (PFS) for Stratum A
Description
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.
Time Frame
Up to 12 months
Title
12 month Overall Survival (OS) for Stratum B
Description
Overall survival will be determined from the date of histological diagnosis to time of death at the 12 month time point.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Frequency of Adverse Events
Description
Toxicity will be described by reporting Adverse Events (AE). Events will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. All study-related and unrelated AEs will be collected and reported, together with their maximum intensity among all recorded respective AE.
Time Frame
From beginning of enrollment up to 30 days post end of treatment.
Title
Frequency of Serious Adverse Events
Description
Toxicity will be described by reporting Serious Adverse Events (SAE). Events will be assessed according to the NCI CTCAE v5.0. All study-related and unrelated Serious Adverse Events (SAE) will be collected and reported, together with their maximum intensity among all recorded respective SAE.
Time Frame
From beginning of enrollment up to 30 days post end of treatment.

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine Mueller, MD, PhD, MAS
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21218
Country
United States
Facility Name
Children's Hospitals and Clinics of Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Children's Hospital Of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data after de-identification.

Learn more about this trial

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

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