ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma.
Evangeline R Jackson, Ryan J Duchatel, Dilana E Staudt...
https://pubmed.ncbi.nlm.nih.gov/37195023Actively Recruiting
Phase 2
Age: 2Years - 39Years
All Genders
ID05009992
Combination Therapy Using an Adaptive Platform for Children and Young Adults with Diffuse Midline Gliomas (DMGs) at Diagnosis, Post-Radiation, and Progression
Led by University of California, San Francisco · Updated on 2025-12-17
360
Participants Needed
32
Research Sites
78 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
Researchers are evaluating the effectiveness of combining ONC201 with other drugs for treating diffuse midline gliomas (DMGs), a group of brain tumors with limited treatment options and poor outcomes. This phase II trial uses an adaptive platform design, opening and closing different treatment arms based on ongoing preclinical results and trial data. The study includes children and young adults aged 2 to 39 with DMGs at various disease stages. Participants are divided into cohorts based on disease stage and treatment history. Some receive escalating doses of ONC201 alone, others receive ONC201 combined with targeted therapies selected by tumor molecular profiling, and another group receives repeated intratumoral injections of DNX-2401, a virus-based therapy. Treatments are given orally or through specialized intratumoral infusions, with dosing schedules adjusted based on safety and pharmacokinetic data. Throughout the study, participants undergo assessments including imaging, tumor biopsies, blood and cerebrospinal fluid tests, and quality of life evaluations. Researchers monitor survival outcomes, treatment side effects, drug concentrations in tumor tissue, and biological markers related to tumor response. Follow-up visits occur every three months for up to five years after treatment to evaluate long-term effects and survival.
CONDITIONS
Brief Title
Combination Therapy for the Treatment of Diffuse Midline Gliomas
Who Can Participate
Age: 2Years - 39Years
All Genders
Eligibility Criteria
You may qualify if you...
- Age between 2 and 39 years
- Diagnosis of diffuse midline glioma (DMG) including spinal cord tumors, confirmed by imaging or pathology
- Recovered from acute side effects of prior therapies and beyond expected toxicity windows
- Body weight at least 10 kilograms
- Adequate organ function including blood counts, kidney, liver, and heart function
- Females of child-bearing potential and males must agree to use contraception
- Karnofsky or Lansky performance score of 50 or higher (70 or higher for Cohort 6)
- Willing to provide tumor tissue samples or biopsy slides
- Specific criteria apply for enrollment into Cohorts 4, 5, and 6 based on treatment history and tumor molecular profile
You will not qualify if you...
- Prior exposure to radiation or re-irradiation for tumor progression in certain cohorts
- Thalamic and cerebellar H3K27M mutant DMG (with some exceptions)
- Diagnosis of histone H3 wildtype grade II diffuse astrocytoma
- Currently receiving other investigational drugs or anti-cancer agents
- Known immune system disorders such as HIV, hepatitis B or C, or autoimmune disease requiring systemic immunosuppression
- Uncontrolled infection or systemic illness
- Pregnant or breastfeeding females
- Active illicit drug use or alcoholism
- History of allergic reactions to study agents
- Evidence of disseminated disease except for Cohort 5
- Use of potent CYP3A4/5 inhibitors or inducers near study drug administration
- For Cohort 6, additional exclusions include tumors outside thalamus/pons, significant mass effect, bleeding risk, immunosuppressive disorders, recent live vaccinations, and others as specified
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to approximately 8 months depending on cohort and treatment phase
Participants receive study treatments including ONC201 alone or in combination with targeted therapies or radiation, or repeated intratumoral DNX-2401 infusions depending on cohort assignment.
Weekly visits during radiation or maintenance phases; DNX-2401 infusions every 30 days for up to 6 injections
Follow-up
Duration - Up to 5 years
After completion of study treatment, participants are followed for safety and survival assessments.
Visits at 30 days post-treatment and every 3 months thereafter
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
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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Published Research Related To This Trial
ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma.
Evangeline R Jackson, Ryan J Duchatel, Dilana E Staudt...
https://pubmed.ncbi.nlm.nih.gov/37145169Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas.
Justyna M Przystal, Chiara Cianciolo Cosentino, Sridevi Yadavilli...
https://pubmed.ncbi.nlm.nih.gov/35157764