Hope for rare brain tumor: phase 3 trial of ONC201 launches

NCT ID NCT05580562

Disease control Sponsor: Jazz Pharmaceuticals Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This Phase 3 trial tests the drug ONC201 (dordaviprone) in people newly diagnosed with a rare brain cancer called H3 K27M-mutant diffuse glioma. Participants receive either ONC201 or a placebo after completing standard radiotherapy. The study aims to see if the drug helps them live longer and delays tumor growth.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Dordaviprone (ONC201)
What this could lead to: If successful, this could provide a new treatment option that extends survival for people with this rare and aggressive brain tumor.
What could go wrong: This is a Phase 3 trial, but the drug may not improve survival compared to placebo. Side effects are possible, and results may not apply to all patients.

This is an AI summary of the original study and may miss details. Read our disclaimer.

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 510 people

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

Started

Jan 2023

Expected to finish

Jun 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

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

Ages

Children (under 18), adults (18 to 64) and older adults (65 and over)

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.

Inclusion Criteria: 1. Able to understand the study procedures and agree to participate in the study by providing written informed consent (by participant or legally authorized representative), and assent when applicable. 2. Body weight ≥ 10 kg at time of randomization. 3. Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a missense K27M mutation in any histone H3-encoding gene detected by testing of tumor tissue (immunohistochemistry \[IHC\] or next-generation sequencing \[NGS\] in a Clinical Laboratory Improvement Amendments \[CLIA\]-certified or equivalent laboratory). \[Site to provide (as available): ≥ 11 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.\] 4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to starting radiotherapy for submission to sponsor's imaging vendor for central read. For participants who had a surgical resection, this scan must be post-resection; for participants who did not have a resection, this scan may be pre- or post-biopsy. 5. At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks after completion of frontline radiotherapy. If unable to obtain contrast-enhanced imaging due to lack of venous access after multiple attempts, a patient may still be eligible after collection of a nonenhanced MRI of the brain. \[Site to also provide all available MRIs completed prior to initiating treatment with study intervention.\] 6. Received frontline radiotherapy 1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma. 2. Completed radiotherapy within 2 to 6 weeks prior to randomization 3. Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33 fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg. 40 Gy in 15 fractions given over approximately 3 weeks). 7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization. 8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day increase (based on dexamethasone dose or equivalent dose of an alternative steroid). Exclusion Criteria: 1. Primary spinal tumor. 2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. 3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination. 4. Any known concurrent malignancy. 5. New lesion(s) outside of the radiation field. 6. Received whole-brain radiotherapy. 7. Received proton therapy for glioma. 8. Use of any of the following treatments within the specified time periods prior to randomization: 1. Dordaviprone (ONC201) or ONC206 at any time. 2. Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma. 3. Temozolomide within past 3 weeks. 4. Tumor treating fields at any time. 5. DRD2 antagonist within past 2 weeks. 6. Any investigational therapy within past 4 weeks. 7. Strong CYP3A4 inhibitors within 3 days. 8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks. 9. Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization: 1. Absolute neutrophil count \< 1.0 × 109/L or platelets \< 75 × 109/L. 2. Total bilirubin \> 1.5 × upper limit of normal (ULN) (participants with Gilbert's syndrome may be included with total bilirubin \> 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN). 3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × ULN. 4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate \< 60 mL/min/1.73 m2). 10. QTc \> 480 msec (based on mean from triplicate electrocardiograms) during screening. 11. Known hypersensitivity to any excipients used in the study intervention formulation. 12. Pregnant, breastfeeding, or planning to become pregnant while receiving study intervention or within 3 months after the last dose. Participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study intervention. 13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy or psychiatric illness/social situations that would limit compliance with study requirements. 14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the investigator, may interfere with participant safety or the ability to complete the study according to the protocol.

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Conditions

The condition(s) this trial relates to.

diffuse midline glioma, H3 K27M-mutant glioma

As listed by the trial registrant

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

GLIOMA H3 K27M

How to take part

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

The places running it

94 sites in 17 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

Aalborg Universitetshospital
RECRUITING

Aalborg, North Denmark, 9000, Denmark
Addenbrooke's Hospital
RECRUITING

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
Albany Medical Center
COMPLETED

Albany, New York, 12208, United States
Asan Medical Center
RECRUITING

Seoul, Seoul Teugbyeolsi, 5505, South Korea
Azienda Ospedaliera Città della Salute e della Scienza di Torino
RECRUITING

Turin, Piedmont, 10126, Italy
BC Cancer - The Vancouver Center
RECRUITING

Vancouver, British Columbia, V5Z 4E6, Canada
Banner MD Anderson Cancer Center
COMPLETED

Phoenix, Arizona, 85006, United States
Barrow Neurological Institute
ACTIVE_NOT_RECRUITING

Phoenix, Arizona, 85013, United States
Beatson West of Scotland Cancer Centre
RECRUITING

Glasgow, Lanarkshire, G12 0YN, United Kingdom
Benefis Hospital Sletten Cancer Institute
WITHDRAWN

Great Falls, Montana, 59405, United States
CHA Bundang Medical Center
RECRUITING

Bundang-Gu, Seongnam-Si, Gyeonggido, 13496, South Korea
Centre Hospitalier Universitaire Vaudois
RECRUITING

Lausanne, Canton of Vaud, 1011, Switzerland
Children's & Women's Health Care of BC
RECRUITING

Vancouver, British Columbia, V6H 0B3, Canada
Children's Healthcare of Atlanta
COMPLETED

Atlanta, Georgia, 30342, United States
Children's Hospital at Montefiore Medical Center
COMPLETED

New York, New York, 10029, United States
Children's Hospital of Orange County
COMPLETED

Orange, California, 92868, United States
Children's Hospital of The King's Daughter
COMPLETED

Norfolk, Virginia, 23507, United States
Childrens Hospital of Eastern Ontario
RECRUITING

Ottawa, Ontario, K1H 8L1, Canada
Churchill Hospital
RECRUITING

Oxford, Ox3 7LE, United Kingdom
Cincinnati Children's Hospital Medical Center
ACTIVE_NOT_RECRUITING

Cincinnati, Ohio, 45229, United States
Clatterbridge Cancer Centre - Liverpool
RECRUITING

Liverpool, Lancashire, L7 8YA, United Kingdom
Cleveland Clinic
ACTIVE_NOT_RECRUITING

Cleveland, Ohio, 44195, United States
Cleveland Clinic Florida
COMPLETED

Weston, Florida, 33331, United States
Clinica Universidad Navarra
RECRUITING

Pamplona, Navarre, 31008, Spain
Columbia University Medical Center
ACTIVE_NOT_RECRUITING

New York, New York, 10032, United States
Complejo Asistencial Universitario de Salamanca - H. Clinico
RECRUITING

Salamanca, 37007, Spain
Copenhagen University Hospital
RECRUITING

Copenhagen, Capital, 2100, Denmark
Dana Farber Cancer Institute
ACTIVE_NOT_RECRUITING

Boston, Massachusetts, 02215, United States
Dell Children's Medical Center of Central Texas
COMPLETED

Austin, Texas, 78723, United States
Duke Cancer Institute
ACTIVE_NOT_RECRUITING

Durham, North Carolina, 27710, United States
Erasmus MC
RECRUITING

Rotterdam, South Holland, 3015 GD, Netherlands
F345 H.C. Andersen's Children's Hospital
RECRUITING

Odense, Region Syddanmark, 5000, Denmark
FLENI Neurologia
RECRUITING

Buenos Aires, C1426ABP, Argentina
Feinberg School of Medicine Northwestern University
ACTIVE_NOT_RECRUITING

Chicago, Illinois, 60611, United States
Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
RECRUITING

Milan, Lombardy, 20133, Italy
Freeman Hospital
RECRUITING

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom
Gangnam Severance Hospital, Yonsei University Health System
RECRUITING

Gangnam, Seoul Teugbyeolsi, 06273, South Korea
Guy's Hospital
RECRUITING

London, SE19RT, United Kingdom
Hadassah Ein Kerem Medical Center
RECRUITING

Jerusalem, 91120, Israel
Hcor Research Institute
RECRUITING

São Paulo, Brazil
Hokkaido University Hospital
RECRUITING

Sapporo, 060-8648, Japan
Hopital Notre Dame, Lachapelle
RECRUITING

Montreal, Quebec, H2X 3E4, Canada
Hospital Clinic de Barcelona
RECRUITING

Barcelona, 08036, Spain
Hospital Infantil Universitario Niño Jesus
RECRUITING

Madrid, 28009, Spain
Hospital Sant Joan de Deu
RECRUITING

Esplugues de Llobregat, Barcelona, 8950, Spain
Hospital Universitari i Politecnic La Fe de Valencia - Adults
RECRUITING

Valencia, 46026, Spain
Hospital Universitari i Politecnic La Fe de Valencia - Pediatrics
RECRUITING

Valencia, 46026, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, 28041, Spain
Hospital Universitario HM Sanchinarro
RECRUITING

Madrid, 28050, Spain
Hospital Universitario Vall d'Hebron
RECRUITING

Barcelona, 8035, Spain
Hospital do GRAACC
RECRUITING

São Paulo, 04023-062, Brazil
Indiana University School of Medicine - Indianapolis
ACTIVE_NOT_RECRUITING

Indianapolis, Indiana, 46202, United States
Inova Schar Cancer Institute
ACTIVE_NOT_RECRUITING

Fairfax, Virginia, 22031, United States
Instituto Do Cancer Do Estado De São Paulo
RECRUITING

São Paulo, Brazil
Istituto Clinico Humanitas
RECRUITING

Rozzano, Lombardy, 20089, Italy
Istituto Nazionale Tumori Regina Elena
WITHDRAWN

Rome, Lazio, 00144, Italy
Istituto Oncologico Veneto
RECRUITING

Padova, Veneto, 35128, Italy
Jersey Shore University Medical Center
ACTIVE_NOT_RECRUITING

Neptune City, New Jersey, 07753, United States
KK Women's and Children's Hospital
RECRUITING

Singapore, 229899, Singapore
Kaiser Permanente Los Angeles Medical Center
COMPLETED

Los Angeles, California, 90027, United States
Kapi'olani Medical Center for Women and Children
COMPLETED

Honolulu, Hawaii, 96826, United States
Klinikum Mannheim Universitätsklinikum gGmbH
RECRUITING

Manheim, 68167, Germany
Klinikum der Johann-Wolfgang Goethe-Universitat
RECRUITING

Frankfurt am Main, Hesse, 60528, Germany
Kyoto University Hospital
RECRUITING

Kyoto, 606-8507, Japan
Laura & Isaac Perlmutter Cancer Center - NYU ACC
ACTIVE_NOT_RECRUITING

New York, New York, 10032-3726, United States
Lenox Hill Hospital
COMPLETED

New York, New York, 10075, United States
Levine Cancer Institute/ Atrium Health
ACTIVE_NOT_RECRUITING

Charlotte, North Carolina, 28204, United States
London Health Sciences Centre
RECRUITING

London, Ontario, N6A 5W9, Canada
Massachusetts General Hospital Cancer Center
ACTIVE_NOT_RECRUITING

Boston, Massachusetts, 02114, United States
Mayo Clinic - Cancer Center - Rochester
ACTIVE_NOT_RECRUITING

Rochester, Minnesota, 55905, United States
Mayo Clinic Arizona
COMPLETED

Phoenix, Arizona, 85054, United States
Mayo Clinic Jacksonville
ACTIVE_NOT_RECRUITING

Jacksonville, Florida, 32224, United States
MedStar Georgetown University Hospital
COMPLETED

Washington D.C., District of Columbia, 20007, United States
Medical University of Vienna - Adults
RECRUITING

Vienna, State of Vienna, 01090, Austria
Medical University of Vienna - Pediatrics
RECRUITING

Vienna, State of Vienna, Austria
Miami Cancer Institute
ACTIVE_NOT_RECRUITING

Miami, Florida, 33176, United States
Moffitt Cancer Center
ACTIVE_NOT_RECRUITING

Tampa, Florida, 33612, United States
Montefiore Medical Park
ACTIVE_NOT_RECRUITING

New York, New York, 10029, United States
National Cancer Center
RECRUITING

Ilsandong-Gu, Goyang-Si, Gyeonggido, 10408, South Korea
National Cancer Center Hospital
RECRUITING

Chūō, 104-0045, Japan
National Cancer Centre
RECRUITING

Singapore, 308433, Singapore
National Hospital Organization Kyushu Cancer Center
RECRUITING

Fukuoka, 812-8582, Japan
National Neuroscience Institute
RECRUITING

Singapore, 308433, Singapore
Neuro-Oncology Associates
ACTIVE_NOT_RECRUITING

Dallas, Texas, 75246, United States
Norton Healthcare
ACTIVE_NOT_RECRUITING

Louisville, Kentucky, 40241, United States
Ochsner Medical Center - New Orleans
COMPLETED

New Orleans, Louisiana, 70121, United States
Odense Universitetshospital
RECRUITING

Odense, Region Syddanmark, 5000, Denmark
Ohio State University
ACTIVE_NOT_RECRUITING

Columbus, Ohio, 43210, United States
Olivia Newton-John Cancer Research Institute (ONJCRI)
RECRUITING

Heidelberg, Victoria, 3084, Australia
Osaka City General Hospital
RECRUITING

Osaka, 534-0021, Japan
Ospedale Bellaria
RECRUITING

Bologna, Emilia-Romagna, 40139, Italy
Ospedale San Raffaele S.r.l.
RECRUITING

Milan, Lombardy, 20132, Italy
Overlook Medical Center
ACTIVE_NOT_RECRUITING

Summit, New Jersey, 07901, United States
Perth Children's Hospital
RECRUITING

Nedlands, Western Australia, 6009, Australia
Phoenix Childrens Hospital
COMPLETED

Phoenix, Arizona, 85016, United States
Princess Margaret Hospital
RECRUITING

Toronto, Ontario, M5G 1X8, Canada
Providence Health and Services St. Vincent Medical Center
ACTIVE_NOT_RECRUITING

Portland, Oregon, 97239, United States
Providence Saint John's Cancer Institute
ACTIVE_NOT_RECRUITING

Santa Monica, California, 90404, United States
Queen Mary Hospital
RECRUITING

Hong Kong, 999077, Hong Kong
Rabin Medical Center
RECRUITING

Petah Tikva, 49372, Israel
Rambam Medical Center
RECRUITING

Haifa, 31096, Israel
Royal Brisbane and Women's Hospital
RECRUITING

Herston, Queensland, Australia
Royal Hobart Hospital
RECRUITING

Hobart, Tasmania, 7000, Australia
Royal Hospital for Children (Glasgow)
RECRUITING

Glasgow, Lanarkshire, G51 4TF, United Kingdom
Royal North Shore Hospital
RECRUITING

Sydney, New South Wales, 2065, Australia
Royal Victoria Infirmary
RECRUITING

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom
Samsung Medical Center
RECRUITING

Gangnam-Gu, Seoul Teugbyeolsi, 06351, South Korea
Schneider Children's Medical Center of Israel
RECRUITING

Petah Tikvah, 4920235, Israel
Seoul National University Bundang Hospital
RECRUITING

Bundang-gu, Seongnam-si, Gyeonggido, 13620, South Korea
Seoul National University Hospital
RECRUITING

Bundang-gu, Seongnam-si, Gyeonggido, 13620, South Korea
Seoul National University Hospital
RECRUITING

Jongno-Gu, Seoul Teugbyeolsi, 03080, South Korea
Severance Hospital Yonsei University Health System
RECRUITING

Seoul, 03722, South Korea
Sheba Medical Center
RECRUITING

Ramat Gan, Tel Aviv, 5262100, Israel
Soroka University Medical Centre
RECRUITING

Beersheba, 50937, Israel
St James University Hospital
RECRUITING

Leeds, West Yorkshire, LS9 7TF, United Kingdom
St Joseph's Children's Hospital of Tampa
COMPLETED

Tampa, Florida, 33607, United States
Stanford Cancer Center
COMPLETED

Stanford, California, 94350, United States
Sunnybrook Health Sciences Centre
RECRUITING

Toronto, Ontario, M4N 3M5, Canada
Sydney Children's Hospital
RECRUITING

Randwick, New South Wales, 2031, Australia
Tel Aviv Sourasky Medical Center
RECRUITING

Tel Aviv, 64239, Israel
The Catholic University of Korea, Seoul St. Mary's Hospital
RECRUITING

Seoul, 6591, South Korea
The Christie NHS Foundation Trust
RECRUITING

Manchester, Lancashire, M20 4BX, United Kingdom
The Leeds Teaching Hospitals NHS Trust, Leeds General Infimary
RECRUITING

Leeds, LS1 3EX, United Kingdom
The Royal Marsden in Sutton, Surrey
RECRUITING

Sutton, Surrey, SM2 5PT, United Kingdom
The University of Tokyo Hospital
RECRUITING

Tokyo, Japan
Thomas Jefferson University
ACTIVE_NOT_RECRUITING

Philadelphia, Pennsylvania, 19107, United States
Tom Baker Cancer Cetre
RECRUITING

Calgary, Alberta, T2N 2T9, Canada
UC San Diego Moores Cancer Center
ACTIVE_NOT_RECRUITING

La Jolla, California, 92093, United States
UCLA University of California Los Angeles
COMPLETED

Los Angeles, California, 90095, United States
UCSF Benioff Children's Hospital
ACTIVE_NOT_RECRUITING

San Francisco, California, 94143, United States
UPMC Children's Hospital of Pittsburgh
COMPLETED

Pittsburgh, Pennsylvania, 15232, United States
UPMC Hillman Cancer Center
COMPLETED

Pittsburgh, Pennsylvania, 15232, United States
UT Health Houston Neurosciences - Texas Medical Center
COMPLETED

Houston, Texas, 77030, United States
Uniklinik Köln
RECRUITING

Cologne, North Rhine-Westphalia, 50937, Germany
Universitair Medisch Centrum Utrecht Cancer Center
RECRUITING

Utrecht, 3584 CX, Netherlands
University Clinic Heidelberg
RECRUITING

Heidelberg, Baden-Wurttemberg, 69120, Germany
University Clinic Regensburg
RECRUITING

Regensburg, Bavaria, 93053, Germany
University Of Wisconsin - Madison
ACTIVE_NOT_RECRUITING

Madison, Wisconsin, 53792, United States
University of California Irvine
ACTIVE_NOT_RECRUITING

Orange, California, 92868, United States
University of California San Francisco
ACTIVE_NOT_RECRUITING

San Francisco, California, 94143, United States
University of Iowa Hospitals & Clinics
ACTIVE_NOT_RECRUITING

Iowa City, Iowa, 52242, United States
University of Maryland School of Medicine
COMPLETED

Baltimore, Maryland, 21201, United States
University of Michigan Hospital
ACTIVE_NOT_RECRUITING

Ann Arbor, Michigan, 48109, United States
University of Minnesota
ACTIVE_NOT_RECRUITING

Minneapolis, Minnesota, 55455, United States
University of Nebraska Medical Center
COMPLETED

Omaha, Nebraska, 68114, United States
University of Oklahoma Peggy and Charles Stephenson Cancer Center
ACTIVE_NOT_RECRUITING

Oklahoma City, Oklahoma, 73104, United States
University of Pennsylvania
ACTIVE_NOT_RECRUITING

Philadelphia, Pennsylvania, 19104, United States
University of Rochester Medical Center
COMPLETED

Rochester, New York, 14642, United States
University of Texas - San Antonio - Health Science Center
ACTIVE_NOT_RECRUITING

San Antonio, Texas, 78229, United States
University of Texas MD Anderson Cancer Center
ACTIVE_NOT_RECRUITING

Houston, Texas, 77030, United States
University of Texas Southwestern Medical Center
ACTIVE_NOT_RECRUITING

Dallas, Texas, 75390, United States
University of Utah - Huntsman Cancer Institute
ACTIVE_NOT_RECRUITING

Salt Lake City, Utah, 84112, United States
University of Washington
ACTIVE_NOT_RECRUITING

Seattle, Washington, 98195, United States
Universitätsklinikum Augsburg
RECRUITING

Augsburg, Bavaria, 86156, Germany
Universitätsklinikum Bonn
RECRUITING

Bonn, North Rhine-Westphalia, 53127, Germany
Universitätsklinikum Essen
RECRUITING

Essen, North Rhine-Westphalia, 45147, Germany
Universitätsklinikum Heidelberg
RECRUITING

Heidelberg, Baden-Wurttemberg, 69120, Germany
Universitätsklinikum Tübingen
RECRUITING

Tübingen, 72076, Germany
Universitätsspital Zürich
RECRUITING

Zurich, 8091, Switzerland
Vivantes Klinikum Neukölln
RECRUITING

Berlin, 12351, Germany
Washington University School of Medicine/St. Louis Children's Hospital
ACTIVE_NOT_RECRUITING

St Louis, Missouri, 63110, United States
Yale University
ACTIVE_NOT_RECRUITING

New Haven, Connecticut, 06511, United States

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