Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0
- Conditions
- Diffuse Intrinsic Pontine GliomaDiffuse Midline Glioma, H3 K27M-Mutant
- Interventions
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 409
Not provided
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
CHU de Bordeaux - Groupe hospitalier Saint André - Hôpital Saint André
🇫🇷Bordeaux, France
CHU de Bordeaux - Groupe hospitalier Pellegrin - Hôpital des enfants
🇫🇷Bordeaux, France
CHRU de Brest - Hôpital Morvan
🇫🇷Brest, France
CHU de Caen - Hôpital Côte de Nacre
🇫🇷Caen, France
CHU Estaing
🇫🇷Clermont-Ferrand, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
CHU François Mitterrand
🇫🇷Dijon, France
CHU Grenoble Alpes - Hôpital Couple-Enfant
🇫🇷Grenoble, France
Centre Oscar Lambret
🇫🇷Lille, France
Hôpital de la mère et de l'enfant
🇫🇷Limoges, France
Centre Léon Bérard
🇫🇷Lyon, France
Hôpital de La Timone
🇫🇷Marseille, France
Hôpital Arnaud de Villeneuve
🇫🇷Montpellier, France
CHRU Nancy - Hôpital central
🇫🇷Nancy, France
CHRU Nancy Brabois - Hôpital d'enfants
🇫🇷Nancy, France
CHU de Nice - Hôpital L'Archet 2
🇫🇷Nice, France
Hôpital Saint Louis
🇫🇷Paris, France
Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix
🇫🇷Paris, France
Institut Curie
🇫🇷Paris, France
CHU Poitiers
🇫🇷Poitiers, France
CHU de Reims - American Memorial Hospital 2
🇫🇷Reims, France
Centre Eugène Marquis
🇫🇷Rennes, France
CHU Rennes - Hôpital Sud
🇫🇷Rennes, France
CHU Rouen Normandie - Hôpital Charles-Nicolle
🇫🇷Rouen, France
CHU de Saint-Etienne - Hôpital Nord
🇫🇷Saint-Étienne, France
Institut de cancérologie Strasbourg Europe (ICANS) - Centre Paul Strauss
🇫🇷Strasbourg, France
Hôpital de Hautepierre
🇫🇷Strasbourg, France
CHRU Tours - Hôpital Clocheville
🇫🇷Tours, France
CHRU Tours - Hôpital Bretonneau
🇫🇷Tours, France
Hospital Universitario Niño Jesus
🇪🇸Madrid, Spain
Hôpital des enfants
🇫🇷Toulouse, France
Karolinska University Hospital
🇸🇪Stockholm, Sweden