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

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

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.

Sponsors & Collaborators

• Innovative Therapies For Children with Cancer Consortium

  collaborator OTHER

• Ministry of Health, France

  collaborator OTHER_GOV

• Jazz Pharmaceuticals

  collaborator INDUSTRY

• Gustave Roussy, Cancer Campus, Grand Paris

  lead OTHER

Principal Investigators

• Jacques GRILL, MD, PhD · Gustave Roussy, Cancer Campus, Grand Paris

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-09-29

Primary Completion

2028-09-30

Completion

2031-09-30

Countries

• Denmark
• France
• Spain
• Sweden

Study Locations