Study of the Efficacy of a New Drug (ONC201) for the Treatment of Brain Tumors Following Radiation Therapy (ACTION Study)

Brain tumors are cancers that can originate from various types of cells in the brain. In diffuse glioma, the cancer originates from supporting cells in the brain—the glial cells (hence “glioma”)—and may exhibit certain genetic changes (mutations). Based on these changes, the tumor is classified into subtypes. This study is investigating diffuse gliomas of the “H3-K27M-mutated” subtype. The disease affects both children and adults and often progresses rapidly.

The standard treatment to date has been radiation therapy; no additional drug therapy has yet been established for this subtype. Therefore, this study is testing treatment with the new drug ONC201 (dordaviprone). It helps selectively kill cancer cells by activating self-destruction processes within the cancer cells. Currently, the drug is used only in clinical trials and has not yet been approved for treatment.

The goal of this Phase 3 study is to investigate whether the additional administration of ONC201 can prolong life expectancy and the time to disease progression following standard treatment.

To this end, patients will be randomly assigned to three groups 2 to 6 weeks after radiation therapy: One group will receive ONC201 twice a week; the second group will receive ONC201 once a week and a placebo on the other days; and the third group will receive only the placebo. A placebo means that the capsule contains no active ingredient. The drug is taken orally in capsule form. The goal of this division is to test the effectiveness of ONC201 and to determine whether a higher or lower dose of the medication works better than a placebo. The study is “double-blind” and “placebo-controlled,” which means that neither the patients nor the treating physicians know who is receiving the drug or a placebo. ONC201 will be administered in the ACTION study for up to 44 months (approximately 3 years and 8 months) or as long as patients benefit from it and no serious side effects occur.

Eligible participants include children and adults of any gender weighing at least 10 kg who have a confirmed diagnosis of an H3-K27M-mutated diffuse glioma and have already completed their initial radiation therapy. Specifically, this means that radiation therapy must have begun within 12 weeks of diagnosis and must have been completed 2 to 6 weeks before study enrollment begins. The disease must also be stable overall, meaning there is no disease activity. Patients with spinal cord involvement are excluded from the study.