ONC201 in Pediatric H3 K27M Gliomas

Recruiting in Palo Alto (17 mi)

+7 other locations

Age: < 65

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Chimerix

No Placebo Group

Trial Summary

What is the purpose of this trial?This trial is testing a new oral medicine called ONC201 in children with specific types of brain tumors that are hard to treat. The medicine works by targeting and killing cancer cells with a particular mutation. The study aims to find the best dose and see how well the medicine works.

Eligibility Criteria

Participant Groups

7Treatment groups

Experimental Treatment

Group I: G (recurrent/refractory H3 K27M-mutant glioma; dosing twice weekly)Experimental Treatment1 Intervention

Pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy will be enrolled to define the RP2D for single agent dordaviprone (ONC201) given on two consecutive days of each week.

Group II: F (recurrent/refractory, progressive high-grade H3 K27M-mutant glioma)Experimental Treatment1 Intervention

Pediatric patients with relapsed/refractory, histologically confirmed high-grade glioma with a known H3 K27M mutation, evidence of progressive disease contrast-enhanced brain MRI as defined by RANO-HGG criteria. Prior therapy with at least radiotherapy is required.

Group III: E (H3 K27M-mutant glioma or DIPG; liquid formulation)Experimental Treatment1 Intervention

Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) or have diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Patients must be 2-12 weeks from completion of first-line radiation. Patients administered liquid formulation of dordaviprone (ONC201) in Ora-Sweet.

Group IV: D (recurrent H3 K27M-mutant glioma; CSF obtained)Experimental Treatment1 Intervention

Pediatric patients with recurrent glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory), have completed at least one line of prior therapy, must be willing to undergo serial lumbar puncture to obtain cerebrospinal fluid (CSF), and must be scheduled to undergo sedated MRIs.

Group V: C (midline glioma)Experimental Treatment1 Intervention

Pediatric patients with midline gliomas are eligible with or without histologic confirmation and must be eligible for tumor biopsy as deemed by the site Investigator.

Group VI: B (newly diagnosed DIPG)Experimental Treatment1 Intervention

Pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. If H3 K27M status of tumor is unknown or archival tumor tissue is not available, then patients must agree to submit a post-mortem biopsy specimen.

Group VII: A (recurrent/refractory H3 K27M-mutant glioma)Experimental Treatment1 Intervention

Pediatric patients with relapsed/refractory glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent/refractory disease.