ONC206 demonstrates potent anti-tumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma.
Theophilos Tzaridis, Jingbo Liu, Franklin Lee Chien...
https://pubmed.ncbi.nlm.nih.gov/41256696Actively Recruiting
Phase 1
Age: 2Years - 21Years
All Genders
ID04732065
Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults With Newly Diagnosed or Recurrent Diffuse Midline Glioma and Other Recurrent Primary Malignant CNS Tumors
Led by Sabine Mueller, MD, PhD · Updated on 2026-03-17
208
Participants Needed
6
Research Sites
8 weeks
Total Duration
On this page
Sponsors
S
Sabine Mueller, MD, PhD
Lead Sponsor
J
Jazz Pharmaceuticals
Collaborating Sponsor
AI-Summary
What this Trial Is About
This research aims to find the best dose and effects of ONC206, a new drug being studied for treating children and young adults with diffuse midline gliomas (DMG) that have a specific genetic alteration (H3K27) or other recurrent malignant tumors in the central nervous system (CNS). The study includes patients who are newly diagnosed, have recurrent disease, or other recurrent malignant CNS tumors. ONC206 may help by triggering a stress response in tumor cells that leads to their death without harming normal cells. Participants are assigned to one of four groups based on their diagnosis and treatment history. Some groups receive ONC206 alone by mouth up to six times a week in 28-day cycles for up to 12 months, with possible extension to 24 months if benefiting. Other groups receive ONC206 combined with standard radiation therapy daily, 5 days a week. Optional imaging scans using proton MR spectroscopy may be done. After treatment, patients have follow-up visits starting 30 days after treatment ends, then every 3 months for up to 5 years. During the study, researchers monitor safety by checking for dose-limiting side effects and find the maximum tolerated dose of ONC206. They also study how the drug moves through the body and tumor tissue, assess tumor response, quality of life, patient satisfaction, and other biological markers. Safety labs, imaging, and neurological evaluations are done regularly. Long-term follow-up helps understand treatment effects over time, and participation may continue under related protocols.
CONDITIONS
Brief Title
ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors
Who Can Participate
Age: 2Years - 21Years
All Genders
Eligibility Criteria
You may qualify if you...
- Children and young adults aged 2 to 21 years with diffuse midline glioma (DMG), H3K27 altered, who completed at least one prior therapy including focal radiation (Arm A)
- Newly diagnosed children and young adults aged 2 years and above with DMG, H3K27 altered, including spinal cord DMGs (Arm B)
- Children and young adults aged 2 years and above with DMGs showing progression and candidates for re-irradiation, with prior focal radiation therapy at least 6 months earlier (Arm C)
- Children and young adults aged 2 years and above with recurrent primary malignant CNS tumors excluding DMGs, with evidence of progression and no prior treatment for this progression (Arm D)
- Tumor tissue confirmation of DMG, H3K27 altered or malignant CNS tumor as applicable
- Recovery from all acute side effects of prior therapy
- Stable or decreasing steroid dose for at least 3 days before registration
- Adequate blood counts and liver and kidney function
- Well-controlled seizure disorder if present
- Use of adequate contraception for males and females of childbearing potential
- Karnofsky or Lansky performance score of 50 or higher
- Willingness to provide adequate tumor tissue
- Ability to understand and sign informed consent or assent
- Enrollment on PNOC COMP if available at site
You will not qualify if you...
- Tumors without pontine or spinal cord epicenter such as thalamic DMG or cerebellar H3K27 altered tumors previously treated with radiation alone (Arms A & B)
- Prior participation in ONC201 upfront trials (Arms C & D), except PNOC022 or expanded access programs
- Current use of other investigational drugs or anti-cancer agents
- Known immune disorders like HIV or hepatitis B or C, or requiring systemic immunosuppressive therapy
- Uncontrolled infections
- Pregnancy or breastfeeding in females of childbearing potential
- Active illicit drug use or alcoholism
- Allergic reactions to compounds similar to ONC206
- Inability to follow study procedures due to language, psychological, or cognitive issues
- Medical conditions affecting ONC206 absorption
- Use of strong CYP3A4, 2D6, 1A2, 2C9, or 2C19 inhibitors or inducers within 14 days prior and during study
- Use of steroids other than inhaled, intranasal, ocular, topical, or non-oral/IV steroids without study team approval
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
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 24 months
Participants receive ONC206 orally up to six times per week, with some participants also undergoing standard of care radiation therapy daily 5 days a week depending on their assigned arm. Treatment cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. If participants benefit from treatment, it may continue up to 24 months.
28-day cycles with treatment days up to six times per week; radiation therapy daily 5 days a week for applicable arms
Follow-up
Duration - Up to 5 years
After completing study treatment, participants are followed up to monitor their health and outcomes, including visits at 30 days post-treatment and every 3 months for up to 5 years.
Visits at 30 days after treatment and every 3 months thereafter
Trial Site Locations
Total: 6 locations
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
2
Emory University
Atlanta, Georgia, United States, 30322
Actively Recruiting
3
University of Michigan
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
4
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
5
Princess Máxima Center for Pediatric Oncology
Utrecht, Netherlands, 3584
Actively Recruiting
6
The University Children's Hospital in Zurich
Zurich, Canton of Zurich, Switzerland, 8032
Actively Recruiting
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Research Team
P
PNOC Operations
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
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https://pubmed.ncbi.nlm.nih.gov/35157764