ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)

ConditionsH3 K27MGlioma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorJazz Pharmaceuticals

About this trial

This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase 3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with dordaviprone (ONC201) following frontline radiotherapy will extend overall survival and progression-free survival in this population. Eligible participants will have histologically diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.

Eligibility criteria

Qualifiers

Able to understand the study procedures and agree to participate in the study by providing written informed consent (by participant or legally authorized representative), and assent when applicable.

Body weight ≥ 10 kg at time of randomization.

Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a missense K27M mutation in any histone H3-encoding gene detected by testing of tumor tissue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a Clinical Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site to provide (as available): ≥ 11 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.]

At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to starting radiotherapy for submission to sponsor's imaging vendor for central read. For participants who had a surgical resection, this scan must be post-resection; for participants who did not have a resection, this scan may be pre- or post-biopsy.

Disqualifiers

Primary spinal tumor.

Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons.

Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.

Any known concurrent malignancy.

Trial design

Treatments tested in this trial

  • Dordaviprone (ONC201)
  • Dordaviprone (ONC201) + Placebo
  • Placebo

Treatment groups

510 Participants
are divided into 3 treatment groups

Sponsors and collaborators

Jazz Pharmaceuticals

Lead sponsor

Chimerix, Inc.

Collaborator