New hope for kids with DIPG: major trial compares two treatments

NCT ID NCT05476939

Disease control Sponsor: Gustave Roussy, Cancer Campus, Grand Paris Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Aug 14, 2026 · Updated 2 times

Summary

This phase 3 trial tests whether the drug ONC201 works better than everolimus for children and adults with DIPG, a rare and aggressive brain tumor. About 433 participants will receive one of the two drugs, and can switch if their disease gets worse. The goal is to see which drug delays tumor growth and extends life.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

About 433 people

The number the study aims to enrol. It can still change while the study runs.

Started

Sep 2022

Expected to finish

Sep 2031

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

6 months and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study: * Diagnosis Criteria: * Diagnosis of DIPG (clinical and radiological). As biopsy is not standard for these tumors, an informed consent is required for the necessary histological verification. \[Biopsy-part of BIOMEDE 2.0 trial\]. OR * Histological diagnosis of DIPG (i.e. H3K28M or EZHIP positive Diffuse Midline Glioma located in the pons) in case the tumor biopsy was performed before study entry. The diagnosis will be defined by 1/ diffuse glioma, 2/ H3K28M mutation or loss of H3K28 trimethylation together with EZHIP overexpression. In this situation, patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR * Molecular diagnosis of DIPG (i.e. H3K28M) in case a liquid biopsy (CSF or blood) was performed before study entry, in a patient who could not undergo a tumor biopsy because it was too dangerous according to the patient's clinical condition. The diagnosis will be defined by 1/ DIPG, 2/ H3K28M mutation. In this situation, patient will sign the consent after the diagnosis to allow collection of the molecular report. OR * Non-DIPG diffuse midline gliomas (ND-DMG), H3K28M mutant or with H3K28 trimethylation loss together with EZHIP overexpression, will be eligible for the trial after biopsy or surgery. As biopsy and surgery is considered as standard practice for these locations, informed consent for the biopsy will not be necessary. Patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR * Non-DIPG diffuse midline gliomas (ND-DMG) will be eligible for the trial before the biopsy in case the diagnosis is clinically or radiologically suspected. Informed consent for the biopsy and molecular analysis will be necessary. Then, if the central pathology review concludes to a ND-DMG with H3K28M mutant or H3K28 trimethylation loss together with EZHIP overexpression, these patients will be eligible for the treatment part of the trial. * Eligible for a biopsy, or biopsy material available for the biomarker assessment. * Age \> 6 months, with no upper age limit. Children between 6 months and 3 years will be discussed on a case by case basis for inclusion in the study for the feasibility of the stereotactic biopsy. * Eligible for cerebral or craniospinal radiotherapy. * Tumor at diagnosis: no prior chemotherapy for the present cancer; no prior cerebral radiation therapy even for another neoplasm. Surgery is allowed when performed for diagnostic or therapeutic purpose. * Metastatic diseases or spinal tumors allowed; in this case, patients would receive craniospinal or spinal radiotherapy and medical treatment (everolimus or ONC201) will be postponed and only started after the end of radiotherapy. * Patients must be affiliated to a social security system or beneficiary of the same according to local requirements. * Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific procedures are conducted according to local, regional or national guidelines. Non eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study: * Uncontrolled spontaneous massive intratumor bleeding. Patients with post-operative bleeding will be allowed to enter the study provided the hemorrhage is controled. Same rule applies for the other post-operative complications (infection, CSF leakage, absence of wound closure, subdural collection…). * Any other concomitant anti-cancer treatment not foreseen by this protocol is not allowed, except corticosteroids and Bevacizumab which are allowed during the protocol. Bevacizumab is not allowed before and until 15 days after the surgery. The use of bevacizumab and corticosteroids will be taken into account when judging the possibility of progression/pseudoprogression. * Any other cancer diagnosed during the last 5 years. * Uncontrolled intercurrent illness or active infection. * Any other co-morbid condition that in the investigator's opinion would impair study participation. * Unable for medical follow-up (geographic, social or mental reasons). * Patient previously treated with irradiation on the brainstem for another neoplasm. * Participation in another clinical study with an investigational product while on study treatment. * Patient under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent. Eligibility criteria for the randomization in BIOMEDE 2.0 study: * Patient enrolled in the BIOMEDE 2.0 study. * Life expectancy \> 12 weeks after the start of study treatment. * Histological diagnosis of DIPG (as per the WHO criteria) confirmed by central pathology review, OR Typical radiology of a DIPG (mandatory central radiological review) as well as the short clinical history (less than three months of pre-existing symptoms) in case of suspected DIPG but no histological confirmation (tumor biopsy performed but not informative), or suspected DIPG with detection of H3K28M mutation in the CSF or blood (ctDNA analysis in the CSF or blood), OR Histological diagnosis of ND-DMG confirmed by central pathology review, with mutation in the histone H3.1, H3.2, H3.3 genes, or loss of H3K28me3 and EZHIP overexpression by immunohistochemistry. * Karnofsky performance status scale or Lansky Play Scale \> 50%. The PS should not take the neurologic deficit per se into account. NB: Children and adults with a worse performance status due to glioma-related motor paresis can be included. * Highly effective and appropriate contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the end of treatment. * Negative pregnancy test (serum beta-HCG or urinary test) evaluated within one week prior randomization in sexually active females of reproductive potential. * Absolute neutrophil count \> 1.0 x 10\^9/l, Platelets \> 100 x 10\^9/l. * Total bilirubin \< 1.5 x ULN, AST and ALT\< 2.5 x ULN. * Serum creatinine \< 1.5 X ULN for age. If serum creatinine \> 1.5 x ULN, creatinine clearance must be \> 70 ml/min/1.73 m² (as per local practice). * Normal coagulation tests within the local reference ranges. * Written informed consent from parents/legal representative, patient, and age-appropriate assent before randomization according to local, regional or national guidelines. Non Eligibility criteria for the randomization in BIOMEDE 2.0 study: * Current organ toxicity \> grade 2 according to the NCI-CTCAE version 5.0, especially cardiovascular or renal disease (including but not limited to: congenital long QT syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment). * Patients with the following cardiac history cannot take ONC201: * Prolongation of QT/QTcF interval (QTc interval \> 480 milliseconds) preferably using Frederica's QT correction formula on two ECGs separated by at least 48 hours. * A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome. * Required concomitant use of medication(s) known to prolong the QT/QTc interval. In this case, patients will be treated in the Everolimus arm without randomization (except if contra-indication to Everolimus). * Pregnant or breastfeeding women. * Patients with chronic HBV disease compatible with the trial are not excluded from the study. These patients randomized to everolimus treatment will have regular viral load monitoring throughout the study. * Patients taking strong P450 inhibitors or inducers or PgP inhibitors are not excluded from the study but drug concentration of everolimus should be monitored carefully to avoid toxicity. Preferably alternative medications should be considered. * Patient with known congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201). * Patients with known hypersensitivity to any component of Everolimus (active substance, other rapamycin derivatives or excipients) will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201). * Patients with known hypersensitivity to any component of ONC201 (drug product or excipients) will not be randomized and will be treated in the Everolimus arm (except if contra-indication to Everolimus).

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Conditions

The condition(s) this trial relates to.

diffuse intrinsic pontine glioma diffuse midline glioma, H3 K27-altered diffuse midline glioma, H3 K27M-mutant

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Diffuse intrinsic pontine glioma Diffuse midline glioma, H3 K27M-mutant Diffuse midline glioma, H3K27-altered

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

53 sites in 6 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

Aarhus Universitetshospital Skejby
RECRUITING

Aarhus, 8200, Denmark
CHRU Nancy - Hôpital central
RECRUITING

Nancy, 54035, France
CHRU Nancy Brabois - Hôpital d'enfants
RECRUITING

Nancy, 54500, France
CHRU Tours - Hôpital Bretonneau
RECRUITING

Tours, 37044, France
CHRU Tours - Hôpital Clocheville
RECRUITING

Tours, 37000, France
CHRU de Brest - Hôpital Morvan
RECRUITING

Brest, 29609, France
CHU Besançon - Hôpital Jean Minjoz
RECRUITING

Besançon, 25030, France
CHU Estaing
RECRUITING

Clermont-Ferrand, 63003, France
CHU François Mitterrand
RECRUITING

Dijon, 21079, France
CHU Grenoble Alpes - Hôpital Albert Michallon
NOT_YET_RECRUITING

Grenoble, 38700, France
CHU Grenoble Alpes - Hôpital Couple-Enfant
RECRUITING

Grenoble, 38700, France
CHU Poitiers
RECRUITING

Poitiers, 86021, France
CHU Rennes - Hôpital Sud
RECRUITING

Rennes, 35203, France
CHU Rouen Normandie - Hôpital Charles-Nicolle
RECRUITING

Rouen, 76000, France
CHU d'Amiens-Picardie Site Sud
RECRUITING

Amiens, 80054, France
CHU d'Angers - Bâtiment Robert Debré
RECRUITING

Angers, 49933, France
CHU de Bordeaux - Groupe hospitalier Pellegrin - Hôpital des enfants
RECRUITING

Bordeaux, 33076, France
CHU de Bordeaux - Groupe hospitalier Saint André - Hôpital Saint André
RECRUITING

Bordeaux, 33000, France
CHU de Caen - Hôpital Côte de Nacre
RECRUITING

Caen, 14033, France
CHU de Nice - Hôpital L'Archet 2
RECRUITING

Nice, 06202, France
CHU de Nice - Hôpital Pasteur 2
RECRUITING

Nice, 06000, France
CHU de Reims - American Memorial Hospital 2
RECRUITING

Reims, 51092, France
CHU de Saint-Denis de La Réunion
RECRUITING

Saint-Denis, 97400, France
CHU de Saint-Etienne - Hôpital Nord
RECRUITING

Saint-Etienne, 42270, France
CHU de Saint-Pierre de La Réunion Sud
RECRUITING

Saint-Pierre, 97488, France
Centre Eugène Marquis
RECRUITING

Rennes, 35042, France
Centre Jean Perrin
RECRUITING

Clermont-Ferrand, 63011, France
Centre Léon Bérard
RECRUITING

Lyon, 69373, France
Centre Oscar Lambret
RECRUITING

Lille, 59020, France
Centre Régional Lutte Contre le Cancer Paul STRAUSS
RECRUITING

Strasbourg, 67065, France
Gustave Roussy
RECRUITING

Villejuif, Val de Marne, 94805, France
H.C. Andersen Children's Hospital, Odense Universitetshospital
RECRUITING

Odense, 5000, Denmark
Helsinki University Hospital
RECRUITING

Helsinki, 00290, Finland
Hospital Universitario Niño Jesus
RECRUITING

Madrid, 28009, Spain
Hospital Universitario y Politécnico de La Fe
RECRUITING

Valencia, 46026, Spain
Hospital Vall D´Hebron
RECRUITING

Barcelona, 8035, Spain
Hôpital Arnaud de Villeneuve
RECRUITING

Montpellier, 34090, France
Hôpital Foch
NOT_YET_RECRUITING

Suresnes, 92150, France
Hôpital Pierre Wertheimer
RECRUITING

Lyon, 69500, France
Hôpital Roger Salengro
NOT_YET_RECRUITING

Lille, 59037, France
Hôpital Saint Louis
RECRUITING

Paris, 75010, France
Hôpital de Hautepierre
RECRUITING

Strasbourg, 67200, France
Hôpital de La Timone
RECRUITING

Marseille, 13005, France
Hôpital de la mère et de l'enfant
RECRUITING

Limoges, 87042, France
Hôpital des enfants
RECRUITING

Toulouse, 31059, France
Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix
RECRUITING

Paris, 75013, France
Institut Curie
RECRUITING

Paris, 75248, France
Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O) - Institut Claudius Regaud
RECRUITING

Toulouse, 31059, France
Institut de Cancérologie de l'Ouest (ICO) - Site Paul Papin
RECRUITING

Angers, 49055, France
Karolinska University Hospital
RECRUITING

Stockholm, 17176, Sweden
Oslo University Hospital, Radiumhospitalet
RECRUITING

Oslo, 0379, Norway
Oslo University Hospital, Rikshospitalet
RECRUITING

Oslo, 0372, Norway
Rigshospitalet
RECRUITING

Copenhagen, 2100, Denmark

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