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NCT05580562Recrutement en cours

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

Fiche officielleVersion simplifiée

Résumé

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.

Critères d'inclusion

1. 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. 2. Body weight ≥ 10 kg at time of randomization. 3. 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). \[Site to provide (as available): ≥ 11 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.\] 4. 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. 5. 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. \[Site to also provide all available MRIs completed prior to initiating treatment with study intervention.\] 6. Received frontline radiotherapy 1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma. 2. Completed radiotherapy within 2 to 6 weeks prior to randomization 3. 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). 7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization. 8. 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).

Critères d'exclusion

1. Primary spinal tumor. 2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. 3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination. 4. Any known concurrent malignancy. 5. New lesion(s) outside of the radiation field. 6. Received whole-brain radiotherapy. 7. Received proton therapy for glioma. 8. Use of any of the following treatments within the specified time periods prior to randomization: 1. Dordaviprone (ONC201) or ONC206 at any time. 2. Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma. 3. Temozolomide within past 3 weeks. 4. Tumor treating fields at any time. 5. DRD2 antagonist within past 2 weeks. 6. Any investigational therapy within past 4 weeks. 7. Strong CYP3A4 inhibitors within 3 days. 8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks. 9. Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization: 1. Absolute neutrophil count \< 1.0 × 109/L or platelets \< 75 × 109/L. 2. 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). 3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × ULN. 4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate \< 60 mL/min/1.73 m2). 10. QTc \> 480 msec (based on mean from triplicate electrocardiograms) during screening. 11. Known hypersensitivity to any excipients used in the study intervention formulation. 12. 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. 13. 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. 14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the investigator, may interfere with participant safety or the ability to complete the study according to the protocol.

Contacts

Les coordonnées de l'équipe de l'essai s'affichent sur demande.

Voir la fiche officielle de l'essai
Statut
Recrutement en cours
Phase
Phase 3
Type d'étude
Interventionnelle
Pays
Suisse, Allemagne, Italie, Autriche, États-Unis, Argentine, Australie, Brésil, Canada, Danemark, Hong Kong, Israël, Japon, Pays-Bas, Singapour, Corée du Sud, Espagne, Royaume-Uni
Promoteur
Jazz Pharmaceuticals(Industrie)
N° de protocole
ONC201-108
Pathologies
H3 K27M, Glioma
Interventions
Médicament, Autre

Traitements évalués

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

Collaborateurs

Chimerix, Inc.

Lieux · 94

  • Lausanne, SuisseCentre Hospitalier Universitaire VaudoisRecrute dans ce centre
  • Zurich, SuisseUniversitätsspital ZürichRecrute dans ce centre
  • Heidelberg, AllemagneUniversity Clinic HeidelbergRecrute dans ce centre
  • Heidelberg, AllemagneUniversitätsklinikum HeidelbergRecrute dans ce centre
  • Augsburg, AllemagneUniversitätsklinikum AugsburgRecrute dans ce centre
  • Regensburg, AllemagneUniversity Clinic RegensburgRecrute dans ce centre
  • Frankfurt am Main, AllemagneKlinikum der Johann-Wolfgang Goethe-UniversitatRecrute dans ce centre
  • Bonn, AllemagneUniversitätsklinikum BonnRecrute dans ce centre
  • Cologne, AllemagneUniklinik KölnRecrute dans ce centre
  • Essen, AllemagneUniversitätsklinikum EssenRecrute dans ce centre
  • Berlin, AllemagneVivantes Klinikum NeuköllnRecrute dans ce centre
  • Manheim, AllemagneKlinikum Mannheim Universitätsklinikum gGmbHRecrute dans ce centre
  • Tübingen, AllemagneUniversitätsklinikum TübingenRecrute dans ce centre
  • Bologna, ItalieOspedale BellariaRecrute dans ce centre
  • Milan, ItalieOspedale San Raffaele S.r.l.Recrute dans ce centre
  • Milan, ItalieFondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo BestaRecrute dans ce centre
  • Rozzano, ItalieIstituto Clinico HumanitasRecrute dans ce centre
  • Turin, ItalieAzienda Ospedaliera Città della Salute e della Scienza di TorinoRecrute dans ce centre
  • Padova, ItalieIstituto Oncologico VenetoRecrute dans ce centre
  • Vienna, AutricheMedical University of Vienna - AdultsRecrute dans ce centre
  • Vienna, AutricheMedical University of Vienna - PediatricsRecrute dans ce centre
  • Buenos Aires, ArgentineFLENI NeurologiaRecrute dans ce centre
  • Randwick, AustralieSydney Children's HospitalRecrute dans ce centre
  • Sydney, AustralieRoyal North Shore HospitalRecrute dans ce centre
  • Herston, AustralieRoyal Brisbane and Women's HospitalRecrute dans ce centre
  • Hobart, AustralieRoyal Hobart HospitalRecrute dans ce centre
  • Heidelberg, AustralieOlivia Newton-John Cancer Research Institute (ONJCRI)Recrute dans ce centre
  • Nedlands, AustraliePerth Children's HospitalRecrute dans ce centre
  • São Paulo, BrésilHospital do GRAACCRecrute dans ce centre
  • São Paulo, BrésilHcor Research InstituteRecrute dans ce centre

Au total, dans le monde, 94 des 162 centres listés au registre recrutent ; les 68 autres ne recrutent pas actuellement.

Statut par centre selon le registre ClinicalTrials.gov (dernière mise à jour publiée : 16 avril 2026).

Ce statut peut avoir changé et ne dit rien de votre éligibilité : avant toute démarche, vérifiez avec votre oncologue ou le centre.

+ 64 autres lieux

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Autres versions

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