Induction of Synthetic Lethality by Activation of Mitochondrial ClpP and Inhibition of HDAC1/2 in Glioblastoma.
Trang T T Nguyen, Enyuan Shang, Salveena Schiffgens...
https://pubmed.ncbi.nlm.nih.gov/35417530Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID04541082
A First-in-human Phase I Single-agent Dose-escalation, Food Effect and Dose Expansion Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Led by Jazz Pharmaceuticals · Updated on 2025-12-18
102
Participants Needed
1
Research Sites
21 weeks
Total Duration
On this page
Sponsors
J
Jazz Pharmaceuticals
Lead Sponsor
N
National Institutes of Health (NIH)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and tolerability of oral ONC206 in patients with recurrent, primary central nervous system (CNS) tumors. This Phase 1, open-label study aims to find the maximum tolerated dose (MTD) and observe dose-limiting toxicities (DLTs) in patients who have no standard treatment options left. The trial includes various rare and recurrent CNS neoplasms such as glioblastoma, anaplastic astrocytoma, ependymoma, and medulloblastoma among others. Participants receive ONC206 orally in escalating dose levels following a 3+3 design over 28-day cycles. Dose adjustments and frequency changes may be made based on safety and pharmacokinetic data. The study includes up to 11 dose levels and approximately 46 patients to determine the MTD. Toxicities are monitored closely during each 28-day treatment cycle, with safety evaluations after each cohort to guide dose escalation decisions. During the study, participants undergo physical exams, vital sign checks, ECGs, blood tests, and adverse event monitoring at every visit. Tumor response is measured using established criteria, and patients provide tumor tissue samples for biomarker analysis. Study staff assess safety, tolerability, and potential toxic effects throughout treatment and for 30 days after the last dose. Total participation duration varies based on dose escalation and individual patient response.
CONDITIONS
Brief Title
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Patients aged 18 years or older with a histologically confirmed recurrent primary CNS neoplasm including glioblastoma, anaplastic astrocytoma, ependymoma, medulloblastoma, and other specified subtypes
- Recurrent and measurable disease after standard treatments with no remaining standard options
- Karnofsky Performance Score of 70 or higher or minimal assistance needed for self-care due to motor deficits
- No prior cytotoxic chemotherapy within 28 days before first dose; specific waiting periods for other therapies apply
- Resolved adverse events from prior therapies except alopecia or neuropathy; Grade 1 or 2 lymphopenia allowed
- No major surgery within 4 weeks prior to first dose and fully recovered from surgery
- Normal organ and marrow function as defined by specified blood counts and liver/kidney function
- Availability of tumor tissue specimen sufficient for biomarker analysis
- Ability to swallow oral capsules or liquids depending on dose level
- Provided informed consent personally; no proxy consent allowed
- Able to tolerate MRI with gadolinium contrast
- Negative COVID-19 test within 72 hours prior to first dose or prior infection under specified conditions
You will not qualify if you...
- History of allergic reactions to ONC206, ONC201, or related compounds
- Uncontrolled illness including active infections or psychiatric/social issues limiting study compliance
- Inability or unwillingness to follow study protocol
- Known HIV positive on antiretroviral therapy
- Active cardiac disease including prolonged QT interval, arrhythmias requiring pacemaker, valvular disease, or symptomatic pericarditis
- Recent myocardial infarction, congestive heart failure, or cardiomyopathy
- Ischemic or hemorrhagic stroke within 3 months
- Refractory epilepsy or recent generalized seizures
- Significant gastrointestinal dysfunction affecting drug absorption
- Recent use of hematopoietic growth factors within 2 weeks
- Use of therapeutic anticoagulants like warfarin
- Use of strong CYP enzyme inhibitors or inducers within 14 days prior to first dose
- Pregnant or breastfeeding women
- Positive pregnancy test within 72 hours prior to first dose
- Concurrent standard or investigational anti-cancer therapy
- Alcohol or substance abuse interfering with safety or compliance
- Serious unstable medical or psychiatric conditions
- Women of childbearing potential or men not agreeing to use highly effective contraception during and 16 weeks after treatment
- Previous receipt of ONC201 or placebo from related studies on or after 01 January 2023 for certain gliomas
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 - Repeated 28-day cycles until dose-limiting toxicity or discontinuation
Participants receive oral ONC206 in escalating doses to determine the maximum tolerated dose and assess safety and tolerability over cycles of 28 days each.
Visits during each 28-day cycle for safety evaluations and assessments
Follow-up
Duration - 30 days
Participants are monitored for safety and adverse events for 30 days after the last dose of study drug.
Approximately 1 to 2 visits after treatment ends
Trial Site Locations
Total: 1 location
1
National Institutes of Health
Bethesda, Maryland, United States, 20892
Actively Recruiting
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Research Team
C
Clinical Trial Disclosure & Transparency
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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