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

Phase 3

Recruiting

• Conditions: Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant
• Interventions: Drug: ONC201; Drug: Everolimus; Radiation: Radiotherapy

• Registration Number: NCT05476939
• Lead Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Brief 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. Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity or consent withdrawal. A switch between treatment groups is allowed after confirmation of the disease progression (real-time central review blinded to the treatment arm allocation).

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-25
• Study First Submitted QC: 2022-07-25
• Study First Posted: 2022-07-27
• Study Start: 2022-09-29
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-13
• Primary Completion: 2028-09
• Study Completion: 2031-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 409

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ONC201	ONC201	Capsules of 125 mg. The prescribed dose is 375 mg/m², once daily at Day 1 and Day 2 of each week. Dose will be capped at 625 mg per dose. Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity, or consent withdrawal. At the time of centrally confirmed progression, patients will stop treatment and will be allowed to switch to the other arm in case no better option is available after considering the results of the molecular profiling. In case of switch (everolimus to ONC201 or vice-versa), the patient will observe a wash-out period before starting: * the second treatment, * or a reirradiation (if applicable). No treatment is allowed during reirradiation. Then, if an additional treatment is needed, the second treatment will be started within one week after the end of the reirradiation.
ONC201	Radiotherapy	Capsules of 125 mg. The prescribed dose is 375 mg/m², once daily at Day 1 and Day 2 of each week. Dose will be capped at 625 mg per dose. Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity, or consent withdrawal. At the time of centrally confirmed progression, patients will stop treatment and will be allowed to switch to the other arm in case no better option is available after considering the results of the molecular profiling. In case of switch (everolimus to ONC201 or vice-versa), the patient will observe a wash-out period before starting: * the second treatment, * or a reirradiation (if applicable). No treatment is allowed during reirradiation. Then, if an additional treatment is needed, the second treatment will be started within one week after the end of the reirradiation.
everolimus	Radiotherapy	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. Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity, or consent withdrawal. At the time of centrally confirmed progression, patients will stop treatment and will be allowed to switch to the other arm in case no better option is available after considering the results of the molecular profiling. In case of switch (everolimus to ONC201 or vice-versa), the patient will observe a wash-out period before starting: * the second treatment, * or a reirradiation (if applicable). No treatment is allowed during reirradiation. Then, if an additional treatment is needed, the second treatment will be started within one week after the end of the reirradiation.
everolimus	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. Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity, or consent withdrawal. At the time of centrally confirmed progression, patients will stop treatment and will be allowed to switch to the other arm in case no better option is available after considering the results of the molecular profiling. In case of switch (everolimus to ONC201 or vice-versa), the patient will observe a wash-out period before starting: * the second treatment, * or a reirradiation (if applicable). No treatment is allowed during reirradiation. Then, if an additional treatment is needed, the second treatment will be started within one week after the end of the reirradiation.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Until 2 years after inclusion of the last patient	Defined as the time between date of randomization and unequivocal clinical, cytological or radiological progression confirmed by central review, or death whatever the cause.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival after first progression	Until 5 years after randomization of the last patient	It will also be computed from the date of progression to the date of subsequent progression or death from any cause, in order to describe the outcome after progression.
Complication rate of the diagnostic biopsy-based procedure	Until 5 years after randomization of the last patient
Duration of the complications (including delay for starting treatment) of the diagnostic biopsy-base procedure	Until 5 years after randomization of the last patient
Safety profile of the drugs	Until 5 years after randomization of the last patient	Using the NCI-CTC v5.0 criteria, during radiotherapy and during the entire duration of the administration of the drug, considering all adverse events except adverse events unequivocally related to the disease (pseudo)-progression.
Overall survival (for the internal comparison between randomized groups)	Until 5 years after randomization of the last patient	Defined from the date of randomization to the date of death from any cause.
Relative benefit/risk ratio of ONC201 compared to everolimus	Until 5 years after randomization of the last patient	It will be assessed using the Q-TWiST approach (Quality-adjusted time without symptoms of disease or adverse event) evaluated from survival times (overall survival and progression-free survival) and adverse events data (date of occurrence of grade 3+ adverse event).
Overall survival (for all the comparisons to historical controls)	Until 5 years after randomization of the last patient	Defined from the date of radiological diagnosis to the date of death from any cause.
Severity of the complications (including prolongation of the hospital stay) of the diagnostic biopsy-based procedure	Until 5 years after randomization of the last patient

Trial Locations

Locations (42)

Aarhus Universitetshospital Skejby; 🇩🇰 Aarhus, Denmark

Hospital Vall D´Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario y Politécnico de La Fe; 🇪🇸 Valence, Spain

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

H.C. Andersen Children's Hospital, Odense Universitetshospital; 🇩🇰 Odense, Denmark

Gustave Roussy; 🇫🇷 Villejuif, Val De Marne, France

CHU d'Amiens-Picardie Site Sud; 🇫🇷 Amiens, France

Institut de Cancérologie de l'Ouest (ICO) - Site Paul Papin; 🇫🇷 Angers, France

CHU d'Angers - Bâtiment Robert Debré; 🇫🇷 Angers, France

CHU Besançon - Hôpital Jean Minjoz; 🇫🇷 Besançon, France

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