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OncoMatch/Clinical Trials/NCT05580562

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

Is NCT05580562 recruiting? Yes, currently enrolling (May 2026). This Phase 3 trial studies Dordaviprone (ONC201) for h3 k27m.

Phase 3RecruitingJazz PharmaceuticalsNCT05580562Data as of May 2026

Treatment: Dordaviprone (ONC201)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 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.

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Extracted eligibility criteria

Cancer type

Glioblastoma

Biomarker criteria

Required: H3F3A (H3 K27M) K27M mutation

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])

Required: HIST1H3B K27M mutation

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])

Prior therapy

Must have received: radiation therapy — frontline

Received frontline radiotherapy

Cannot have received: whole-brain radiotherapy

Received whole-brain radiotherapy

Cannot have received: proton therapy

Received proton therapy for glioma

Cannot have received: ONC201 (ONC201)

ONC201 at any time

Cannot have received: ONC206 (ONC206)

ONC206 at any time

Cannot have received: anti-VEGF therapy (bevacizumab)

Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma

Cannot have received: alkylating agent (temozolomide)

Temozolomide within past 3 weeks

Cannot have received: tumor treating fields

Tumor treating fields at any time

Cannot have received: dopamine receptor D2 antagonist

DRD2 antagonist within past 2 weeks

Cannot have received: investigational therapy

Any investigational therapy within past 4 weeks

Lab requirements

Blood counts

Absolute neutrophil count ≥ 1.0 × 10^9/L; platelets ≥ 75 × 10^9/L

Kidney function

Creatinine clearance > 60 mL/min as calculated by Cockcroft Gault equation (or eGFR ≥ 60 mL/min/1.73 m2)

Liver function

Total bilirubin ≤ 1.5 × ULN (participants with Gilbert's syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN); AST or ALT ≤ 2.5 × ULN

Cardiac function

QTc ≤ 480 msec (mean from triplicate ECGs)

Absolute neutrophil count < 1.0 × 10^9/L or platelets < 75 × 10^9/L [excluded]. Total bilirubin > 1.5 × ULN (participants with Gilbert's syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN) [excluded]. AST or ALT > 2.5 × ULN [excluded]. Creatinine clearance ≤ 60 mL/min as calculated by Cockcroft Gault equation (or eGFR < 60 mL/min/1.73 m2) [excluded]. QTc > 480 msec (mean from triplicate ECGs) [excluded].

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Banner MD Anderson Cancer Center · Phoenix, Arizona
  • Barrow Neurological Institute · Phoenix, Arizona
  • Phoenix Childrens Hospital · Phoenix, Arizona
  • Mayo Clinic Arizona · Phoenix, Arizona
  • UC San Diego Moores Cancer Center · La Jolla, California

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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