Health TrialsbyHealthPanel

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

This trial does not accept healthy volunteers

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

Design model

Parallel

Treatments tested in this trial

  • Dordaviprone (ONC201)

    Drug

    Participants ≥ 52.5 kg will receive 625 mg of dordaviprone (5 × 125-mg capsules) dosing days; participants \< 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments.

  • Dordaviprone (ONC201) + Placebo

    Drug

    Participants ≥ 52.5 kg will receive 625 mg of dordaviprone (5 × 125-mg capsules) or matching placebo on dosing days; participants \< 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments

  • Placebo

    Other intervention

    Participants will receive placebo (same number of capsules as the dordaviprone dose) on dosing days

Treatment groups

510 Participants
are divided into 3 treatment groups
Group A: Dordaviprone Twice Weekly GroupExperimental treatment 1 intervention
Group B: Dordaviprone Once Weekly GroupExperimental treatment 1 intervention
Group C: Placebo GroupPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Overall survival (OS)

Overall Survival is defined as the time from randomization to death due to any cause.

Time frame
From date of randomization until date of death from any cause, assessed up to approximately 44 months

Secondary outcomes

1

Progression Free Survival (PFS) using RANO 2.0 Criteria for All Participants

PFS is defined as time from randomization to disease progression (PD) or death.

Time frame
From date of randomization until the date of first documented progression assessed up to approximately 44 months.
2

PFS Using RANO 2.0 Criteria for Participants with Measurable Contrast-Enhancing Disease

PFS is defined as time from randomization to disease progression (PD) or death.

Time frame
From date of randomization up to 44 months
3

Incidence of adverse events

Incidence of overall, treatment-related, Grade 3 or higher in severity, serious, fatal, those resulting in treatment discontinuation, and events of special interest

Time frame
From date of randomization up to 44 months
4

Change from baseline in clinical laboratory parameters

Percentage of participants with clinically significant laboratory results

Time frame
From date of randomization up to 44 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Jazz Pharmaceuticals

Lead sponsor

Chimerix, Inc.

Collaborator

Source ClinicalTrials.gov
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