Actively Recruiting

Phase 2
Age: 2Years - 39Years
All Genders
NCT05009992

Combination Therapy for the Treatment of Diffuse Midline Gliomas

Led by University of California, San Francisco · Updated on 2025-12-17

360

Participants Needed

32

Research Sites

401 weeks

Total Duration

On this page

Sponsors

U

University of California, San Francisco

Lead Sponsor

T

The Chad-Tough Defeat DIPG Foundation

Collaborating Sponsor

AI-Summary

What this Trial Is About

This phase II trial determines if the combination of ONC201 with different drugs is effective for treating participants with diffuse midline gliomas (DMGs). Despite years of research, little to no progress has been made to improve outcomes for participants with DMGs, and there are few treatment options. This trial will utilize an adaptive platform design in that the different treatment arms for each cohort will be opened and closed based on ongoing preclinical investigation as well as evolving outcome data from the trial. Novel agents will be continuously added to this study as pre-clinical data emerge to suggest additive or synergistic activity when combined ONC201. Should a novel agent not have an RP2D at the time of incorporation into this study, a phase 1 lead-in will be performed prior to initiation of combination therapy (via study amendment).

CONDITIONS

Official Title

Combination Therapy for the Treatment of Diffuse Midline Gliomas

Who Can Participate

Age: 2Years - 39Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 2 and 39 years
  • Diagnosis of diffuse midline glioma (DMG) or diffuse intrinsic pontine glioma (DIPG) confirmed by imaging or pathology
  • Recovered from acute side effects of prior therapies and beyond expected ongoing toxicities
  • Body weight of at least 10 kilograms
  • Willingness to provide adequate tumor tissue samples
  • Stable or decreasing corticosteroid dose prior to baseline MRI
  • Adequate organ function including blood counts, kidney and liver function, and cardiac health
  • Female participants of child-bearing potential and males must agree to use contraception
  • Karnofsky or Lansky performance score of at least 50 for participants over 16 years or 16 and under respectively
  • For Cohort 6, participants must be within 4-14 weeks after completing radiation therapy and have thalamic or pontine DMG
  • Prior use of temozolomide during radiation allowed under defined dosing conditions
Not Eligible

You will not qualify if you...

  • Prior exposure to radiation therapy or re-irradiation depending on cohort
  • Thalamic and cerebellar H3K27M mutant DMG except under specific conditions
  • Diagnosis of histone H3 wildtype grade II diffuse astrocytoma
  • Currently receiving other investigational or anti-cancer agents
  • Known immune disorders requiring systemic immunosuppressive therapy
  • Uncontrolled infections or systemic illnesses
  • Pregnant or breastfeeding females
  • Active illicit drug use or alcoholism
  • History of allergic reactions to study agents
  • Evidence of disseminated or multifocal disease not allowed except in Cohort 5
  • Additional malignancies requiring active treatment within 3 years
  • Use of potent CYP3A4/5 inhibitors or inducers around study drug administration
  • For Cohort 6, exclusion includes tumors outside thalamus or pons, significant mass effect or herniation, bleeding risks, active viral infections, immunosuppressive disorders, recent live vaccinations, and disseminated disease

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 32 locations

1

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

Actively Recruiting

2

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

Actively Recruiting

3

University of California, San Diego / Rady Children's Hospital, San Diego

San Diego, California, United States, 92123

Actively Recruiting

4

University of California, San Francisco

San Francisco, California, United States, 94143

Actively Recruiting

5

Children's National Hospital

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

Actively Recruiting

6

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

Chicago, Illinois, United States, 60611

Actively Recruiting

7

Indiana University Riley Children's Hospital

Indianapolis, Indiana, United States, 46202

Actively Recruiting

8

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Actively Recruiting

9

Dana-Farber Cancer Institute Harvard University

Boston, Massachusetts, United States, 02215-6024

Actively Recruiting

10

University of Michigan

Ann Arbor, Michigan, United States, 48109

Actively Recruiting

11

Children's Hospital Minnesota

Minneapolis, Minnesota, United States, 55404

Actively Recruiting

12

Washington University in St. Louis

St Louis, Missouri, United States, 63110

Actively Recruiting

13

Hackensack Meridian Health

Hackensack, New Jersey, United States, 07601

Actively Recruiting

14

New York University

New York, New York, United States, 10016

Actively Recruiting

15

Duke University

Durham, North Carolina, United States, 27708

Actively Recruiting

16

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Actively Recruiting

17

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Actively Recruiting

18

University of Utah

Salt Lake City, Utah, United States, 84101

Actively Recruiting

19

Seattle Children's Hospital

Seattle, Washington, United States, 98101

Actively Recruiting

20

John Hunter Children's Hospital

New Lambton Heights, New South Wales, Australia, 2305

Actively Recruiting

21

The Children's Hospital at Westmead

Westmead, New South Wales, Australia, 2152

Actively Recruiting

22

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Actively Recruiting

23

Monash Children's Hospital

Clayton, Victoria, Australia, 3168

Actively Recruiting

24

The Royal Children's Hospital Melbourne

Melbourne, Victoria, Australia, 3052

Actively Recruiting

25

Perth Children's Hospital

Nedlands, Washington, Australia, 6009

Actively Recruiting

26

Women and Children's Hospital

Adelaide, Australia

Actively Recruiting

27

Sydney Children's Hospital

Sydney, Australia, 2031

Actively Recruiting

28

Sheba Medical Center

Tel Litwinsky, Ramat Gan, Israel

Actively Recruiting

29

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Actively Recruiting

30

Princess Maxima Center

Utrecht, Netherlands

Active, Not Recruiting

31

Starship Children's Hospital

Auckland, New Zealand

Actively Recruiting

32

The University Children's Hospital in Zurich

Zurich, Switzerland

Actively Recruiting

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Research Team

K

Kelly Hitchner

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

6

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