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

Recruiting now · Phase 3 · Has a placebo group

Conditions studied: H3 K27M, Glioma

In brief

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.

Key facts

Study ID

NCT05580562

Run by

Jazz Pharmaceuticals

People needed

510

Starts

2023-01-23

Expected to finish

2028-06-01

Last updated by the study team

2026-04-16

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks after completion of frontline radiotherapy. If unable to obtain contrast-enhanced imaging due to lack of venous access after multiple attempts, a patient may still be eligible after collection of a nonenhanced MRI of the brain. [Site to also provide all available MRIs completed prior to initiating treatment with study intervention.]
• Received frontline radiotherapy
• Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma.
• Completed radiotherapy within 2 to 6 weeks prior to randomization
• Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33 fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg. 40 Gy in 15 fractions given over approximately 3 weeks).
• Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization.
• Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day increase (based on dexamethasone dose or equivalent dose of an alternative steroid).

You may not qualify if…

• 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.
• New lesion(s) outside of the radiation field.
• Received whole-brain radiotherapy.
• Received proton therapy for glioma.
• Use of any of the following treatments within the specified time periods prior to randomization:
• Dordaviprone (ONC201) or ONC206 at any time.
• Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma.
• Temozolomide within past 3 weeks.
• Tumor treating fields at any time.
• DRD2 antagonist within past 2 weeks.
• Any investigational therapy within past 4 weeks.
• Strong CYP3A4 inhibitors within 3 days.
• Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks.
• Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization:
• Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L.
• Total bilirubin > 1.5 × upper limit of normal (ULN) (participants with Gilbert's syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.
• Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate < 60 mL/min/1.73 m2).
• QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening.
• Known hypersensitivity to any excipients used in the study intervention formulation.
• Pregnant, breastfeeding, or planning to become pregnant while receiving study intervention or within 3 months after the last dose. Participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study intervention.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy or psychiatric illness/social situations that would limit compliance with study requirements.

Where it is running

• Children's & Women's Health Care of BC — Vancouver, British Columbia, Canada (enrolling)
• Odense Universitetshospital — Odense, Region Syddanmark, Denmark (enrolling)
• Perth Children's Hospital — Nedlands, Western Australia, Australia (enrolling)
• BC Cancer - The Vancouver Center — Vancouver, British Columbia, Canada (enrolling)
• Hopital Notre Dame, Lachapelle — Montreal, Quebec, Canada (enrolling)
• F345 H.C. Andersen's Children's Hospital — Odense, Region Syddanmark, Denmark (enrolling)
• Royal North Shore Hospital — Sydney, New South Wales, Australia (enrolling)
• Olivia Newton-John Cancer Research Institute (ONJCRI) — Heidelberg, Victoria, Australia (enrolling)
• Hospital do GRAACC — São Paulo, Brazil (enrolling)
• Tom Baker Cancer Cetre — Calgary, Alberta, Canada (enrolling)
• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (enrolling)
• Princess Margaret Hospital — Toronto, Ontario, Canada (enrolling)
• Copenhagen University Hospital — Copenhagen, Capital, Denmark (enrolling)
• Aalborg Universitetshospital — Aalborg, North Denmark, Denmark (enrolling)
• FLENI Neurologia — Buenos Aires, Argentina (enrolling)
• Sydney Children's Hospital — Randwick, New South Wales, Australia (enrolling)
• Royal Brisbane and Women's Hospital — Herston, Queensland, Australia (enrolling)
• Royal Hobart Hospital — Hobart, Tasmania, Australia (enrolling)
• Medical University of Vienna - Adults — Vienna, State of Vienna, Austria (enrolling)
• Medical University of Vienna - Pediatrics — Vienna, State of Vienna, Austria (enrolling)
• Hcor Research Institute — São Paulo, Brazil (enrolling)
• Instituto Do Cancer Do Estado De São Paulo — São Paulo, Brazil (enrolling)
• London Health Sciences Centre — London, Ontario, Canada (enrolling)
• Childrens Hospital of Eastern Ontario — Ottawa, Ontario, Canada (enrolling)
• University Clinic Heidelberg — Heidelberg, Baden-Wurttemberg, Germany (enrolling)

Full record on ClinicalTrials.gov

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