A Study of ONC201 for Refractory Meningioma

NCT06012929 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 0137-24-FB
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn about treatment for a type of brain tumor called a meningioma. This study will enroll two groups of people. One group will be for people who will receive surgery to remove their brain tumor. The other group will be for people who have previously received treatment for their brain tumor but do not have any other available options for treatment. The primary goals of this study are:

1. 1.To measure how much of the study drug is present in tumor tissue taken from patients during surgery to remove their brain tumor
2. 2.To measure the length of time between a study participant's first dose of study treatment until the time when their brain tumor gets worse or their death

Conditions

Meningioma; Refractory Meningioma; Relapsed Meningioma

Outcome Measures

Primary Outcomes (2)

• Evaluation of ONC201 concentration in resected meningioma tissue

  Tumor tissue will be collected from Arm I participants at the time of surgical resection. The samples will be analyzed for the concentration of ONC201 in the tissue.

  Up to 12 months

• Evaluation of progression-free survival (PFS)

  PFS at 6 months will be evaluated in participants assigned to Arm II. PFS is defined as the time from the start of study treatment to the time of disease progression or death. Participants without progression and who are alive at the time of last follow-up will be censored.

  Up to 18 months

Secondary Outcomes (3)

• Evaluation of tumor response from ONC201 on imaging

  Up to 24 months

• Correlation of DRD2 expression with tumor response

  Up to 12 months

• Evaluation of the efficacy of adding bevacizumab to ONC201 following disease progression

  Up to 24 months

Study Arms (2)

Arm I - Presurgical

EXPERIMENTAL

Participants who will be undergoing surgery to remove their meningioma will receive two doses of ONC201 prior to their surgery. ONC201 is taken by mouth at 625 mg per dose. ONC201 will be taken once per week with the second dose taken approximately 24 hours prior to surgery.

Drug: ONC201

Arm II - ONC201 treatment only

EXPERIMENTAL

Participants will receive one dose of ONC201 per week until progression. ONC201 is taken by mouth at 625 mg per dose.

Drug: ONC201

Interventions

ONC201 DRUG

ONC201 is an oral medication given once per week

Also known as: dordaviprone

Arm I - Presurgical; Arm II - ONC201 treatment only

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For both study arms:
• Brain imaging demonstrating a meningioma for which resection has been recommended (Arm I) or any subject with pathologically proven meningioma without reasonable surgical options for complete resection, or reasonable radiation therapy options, determined by neurosurgery and radiation oncology opinions (Arm II)
• Age \> 18 years old at time of study entry (consent) or adult male or female (For Nebraska, age of consent is ≥19 years old)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to treatment (cycle 1 day 1, C1D1)
• Hemoglobin \>8.0 mg/dL without red blood cell transfusion ≤ 3 days prior to C1D1
• Total serum bilirubin \<1.5 X upper limit of normal (ULN), except in cases of Gilbert's disease
• Aspartate aminotransferase (AST) (SGOT)/Alanine transaminase (ALT) (SGPT) ≤2 X ULN secondary to tumor
• Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2)
• Ability to understand and the willingness to sign a written informed consent document.
• Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception while on ONC201 and for at least 90 days after completion of treatment. Male subjects must be surgically sterile or must agree to use effective contraception while on ONC201 and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• Any number of prior medical therapies is allowed but not required.
• Multifocal disease is allowed.
• Subjects with history of neurofibromatosis may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months.

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 28 days.
• Active chemotherapy, including other investigational agents within 28 days of study treatment.
• Craniotomy or other major surgery within 28 days of registration.
• Evidence of metastatic meningiomas (as defined by extracranial meningiomas).
• Known active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV).
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, or cerebrovascular accident. Subjects planning to continue on study after progression with the addition of bevacizumab cannot have uncontrolled hypertension, nephrotic syndrome, or had a history of intracranial bleeding or GI hemorrhage in the last 6 months.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the subject inappropriate for entry into the study.
• Concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers. Subject must discontinue the drug for 14 days prior to registration.
• Prolongation of QT/corrected QT interval by Fridericia (QT/QTcF) interval (QTc interval \>480 milliseconds) using Frederica's QT correction formula on two ECGs separated by at least 48 hours.
• A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome.
• Concomitant use of medication(s) known to prolong the QT/QTc interval.

Sponsors & Collaborators

• University of Nebraska: lead
• Jazz Pharmaceuticals: collaborator

MeSH Terms

Conditions

Meningioma

Interventions

TIC10 compound

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Nicole Shonka, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 28, 2023
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 26, 2026

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share