NCT05476939

Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0

Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 433 (estimated)
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris · Academic / Other
• Sex: All
• Age: 6 Months
• Healthy volunteers: Not accepted

Summary

The BIOMEDE 2.0 study is the second stage of the BIOMEDE multi-arm, multistage rolling programme (adaptive platform protocol). It is a multicenter, randomized, open-label, controlled phase-3 trial evaluating efficacy of ONC201 in comparison with everolimus (primary objective based on internal comparison) and subsequently to historical controls. Two treatment groups will be compared. A switch between treatment groups is allowed after confirmation of the disease progression (real-time central review blinded to the treatment arm allocation). Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity or consent withdrawal. The final conclusion of the trial will be successful for ONC201, if ONC201 is found significantly superior to everolimus in terms of centrally-reviewed PFS (Progression-free survival) from randomization (internal comparison) either overall, considering ND-DMG and DIPG-patients together, or in the subgroup of ND-DMG patients alone. In other cases, Everolimus will remain the standard arm unless it appears associated with an excess of toxicity compared to ONC201 which could then be discussed as a new standard.

Conditions

• Diffuse Intrinsic Pontine Glioma
• Diffuse Midline Glioma, H3 K27M-Mutant
• Diffuse Midline Glioma, H3K27-altered

Interventions

Type	Name	Description
DRUG	Everolimus	Tablets of 2.5 mg or 10 mg. The prescribed dose is 5 mg/m²/day, orally, once daily. Dose will be capped at 10 mg once daily.
DRUG	ONC201	Capsules of 125mg. The prescribed dose is 375mg/m², orally, once daily at Day 1 and Day 2 of each week. Dose will be capped at 625 mg per dose.
RADIATION	Radiotherapy	All patients will be treated with 30 conventional single daily fractions of 1.8 Gy to a total of 54 Gy over a planned period of 6 weeks. Dose may be increased up to 60 Gy for adult patients with supratentorial ND-DMG. The clinical target volume will include all the areas of abnormality on T2/FLAIR sequences with a 1-cm margin. Radiotherapy will have to start within a maximum of 4 weeks for DIPG, up to 6 weeks for other DMG H3K28-altered (ND-DMG), after the biopsy or last surgery. The study medication will be started at Day 1 (+3 days max) of radiotherapy. Reirradiation is permitted only at disease progression according to local practice. In case of metastatic disease or intramedullary tumors, patients can be included in the study. In this situation, radiotherapy will have to start within a maximum of 4 weeks for DIPG, up to 6 weeks for other DMG H3K28-altered (ND-DMG), after the biopsy or last surgery while targeted treatment will start at the end of the irradiation.

Timeline

• Start date: 2022-09-29
• Primary completion: 2028-09-01
• Completion: 2031-09-01
• First posted: 2022-07-27
• Last updated: 2026-02-05

Locations

50 sites across 4 countries: Denmark, France, Spain, Sweden