Testing Dordaviprone against a placebo for H3 K27M

Exclusion

• −Known hypersensitivity to any excipients used in the study intervention formulation.
• −Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
• −Primary spinal tumor.
• −Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons.
• −Any known concurrent malignancy.
• −Received whole-brain radiotherapy.
• −Received proton therapy for glioma.
• −Use of any of the following treatments within the specified time periods prior to randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →:
• −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 screeningScreeningThe checks done before joining, to see whether a study fits.Read more →.
• −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.
• −Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, may interfere with participant safety or the ability to complete the study according to the protocolProtocolThe detailed plan a study must follow.Read more →.
• −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.
• −New lesion(s) outside of the radiation field.