ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)
ACTION
ONC201 for the Treatment of Newly Diagnosed H3 K27M-mutant Diffuse Glioma Following Completion of Radiotherapy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
1 other identifier
interventional
510
17 countries
156
Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase 3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with dordaviprone (ONC201) following frontline radiotherapy will extend overall survival and progression-free survival in this population. Eligible participants will have histologically diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2023
Longer than P75 for phase_3
156 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 27, 2022
CompletedFirst Posted
Study publicly available on registry
October 14, 2022
CompletedStudy Start
First participant enrolled
January 23, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2028
April 16, 2026
April 1, 2026
5.4 years
September 27, 2022
April 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival (OS)
Overall Survival is defined as the time from randomization to death due to any cause.
From date of randomization until date of death from any cause, assessed up to approximately 44 months
Secondary Outcomes (22)
Progression Free Survival (PFS) using RANO 2.0 Criteria for All Participants
From date of randomization until the date of first documented progression assessed up to approximately 44 months.
PFS Using RANO 2.0 Criteria for Participants with Measurable Contrast-Enhancing Disease
From date of randomization up to 44 months
Incidence of adverse events
From date of randomization up to 44 months
Change from baseline in clinical laboratory parameters
From date of randomization up to 44 months
Distribution of Graded Clinical Laboratory Parameter
From date of randomization up to 44 months
- +17 more secondary outcomes
Study Arms (3)
Dordaviprone Twice Weekly Group
EXPERIMENTALDordaviprone Once Weekly Group
EXPERIMENTALPlacebo Group
PLACEBO COMPARATORInterventions
Participants ≥ 52.5 kg will receive 625 mg of dordaviprone (5 × 125-mg capsules) dosing days; participants \< 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments.
Participants ≥ 52.5 kg will receive 625 mg of dordaviprone (5 × 125-mg capsules) or matching placebo on dosing days; participants \< 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments
Participants will receive placebo (same number of capsules as the dordaviprone dose) on dosing days
Eligibility Criteria
You may qualify if:
- 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.
- Body weight ≥ 10 kg at time of randomization.
- 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). \[Site to provide (as available): ≥ 11 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.\]
- 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.
- 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. \[Site to also provide all available MRIs completed prior to initiating treatment with study intervention.\]
- Received frontline radiotherapy
- Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma.
- Completed radiotherapy within 2 to 6 weeks prior to randomization
- 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).
- Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization.
- 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).
You may not qualify if:
- Primary spinal tumor.
- Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons.
- Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
- Any known concurrent malignancy.
- New lesion(s) outside of the radiation field.
- Received whole-brain radiotherapy.
- Received proton therapy for glioma.
- Use of any of the following treatments within the specified time periods prior to randomization:
- Dordaviprone (ONC201) or ONC206 at any time.
- Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma.
- Temozolomide within past 3 weeks.
- Tumor treating fields at any time.
- DRD2 antagonist within past 2 weeks.
- Any investigational therapy within past 4 weeks.
- Strong CYP3A4 inhibitors within 3 days.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jazz Pharmaceuticalslead
- Chimerix, Inc.collaborator
Study Sites (162)
Banner MD Anderson Cancer Center
Phoenix, Arizona, 85006, United States
Barrow Neurological Institute
Phoenix, Arizona, 85013, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027, United States
UCLA University of California Los Angeles
Los Angeles, California, 90095, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
University of California Irvine
Orange, California, 92868, United States
UCSF Benioff Children's Hospital
San Francisco, California, 94143, United States
University of California San Francisco
San Francisco, California, 94143, United States
Providence Saint John's Cancer Institute
Santa Monica, California, 90404, United States
Stanford Cancer Center
Stanford, California, 94350, United States
Yale University
New Haven, Connecticut, 06511, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
St Joseph's Children's Hospital of Tampa
Tampa, Florida, 33607, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Cleveland Clinic Florida
Weston, Florida, 33331, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342, United States
Kapi'olani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Feinberg School of Medicine Northwestern University
Chicago, Illinois, 60611, United States
Indiana University School of Medicine - Indianapolis
Indianapolis, Indiana, 46202, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242, United States
Norton Healthcare
Louisville, Kentucky, 40241, United States
Ochsner Medical Center - New Orleans
New Orleans, Louisiana, 70121, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic - Cancer Center - Rochester
Rochester, Minnesota, 55905, United States
Washington University School of Medicine/St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
Benefis Hospital Sletten Cancer Institute
Great Falls, Montana, 59405, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68114, United States
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753, United States
Overlook Medical Center
Summit, New Jersey, 07901, United States
Albany Medical Center
Albany, New York, 12208, United States
Children's Hospital at Montefiore Medical Center
New York, New York, 10029, United States
Montefiore Medical Park
New York, New York, 10029, United States
Laura & Isaac Perlmutter Cancer Center - NYU ACC
New York, New York, 10032-3726, United States
Columbia University Medical Center
New York, New York, 10032, United States
Lenox Hill Hospital
New York, New York, 10075, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
Levine Cancer Institute/ Atrium Health
Charlotte, North Carolina, 28204, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Ohio State University
Columbus, Ohio, 43210, United States
University of Oklahoma Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Providence Health and Services St. Vincent Medical Center
Portland, Oregon, 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15232, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Neuro-Oncology Associates
Dallas, Texas, 75246, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
UT Health Houston Neurosciences - Texas Medical Center
Houston, Texas, 77030, United States
University of Texas - San Antonio - Health Science Center
San Antonio, Texas, 78229, United States
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Children's Hospital of The King's Daughter
Norfolk, Virginia, 23507, United States
University of Washington
Seattle, Washington, 98195, United States
University Of Wisconsin - Madison
Madison, Wisconsin, 53792, United States
FLENI Neurologia
Buenos Aires, C1426ABP, Argentina
Sydney Children's Hospital
Randwick, New South Wales, 2031, Australia
Royal North Shore Hospital
Sydney, New South Wales, 2065, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Olivia Newton-John Cancer Research Institute (ONJCRI)
Heidelberg, Victoria, 3084, Australia
Perth Children's Hospital
Nedlands, Western Australia, 6009, Australia
Medical University of Vienna - Adults
Vienna, State of Vienna, 01090, Austria
Medical University of Vienna - Pediatrics
Vienna, State of Vienna, Austria
Hospital do GRAACC
São Paulo, 04023-062, Brazil
Hcor Research Institute
São Paulo, Brazil
Instituto Do Cancer Do Estado De São Paulo
São Paulo, Brazil
Tom Baker Cancer Cetre
Calgary, Alberta, T2N 2T9, Canada
BC Cancer - The Vancouver Center
Vancouver, British Columbia, V5Z 4E6, Canada
Children's & Women's Health Care of BC
Vancouver, British Columbia, V6H 0B3, Canada
London Health Sciences Centre
London, Ontario, N6A 5W9, Canada
Childrens Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G 1X8, Canada
Hopital Notre Dame, Lachapelle
Montreal, Quebec, H2X 3E4, Canada
Copenhagen University Hospital
Copenhagen, Capital, 2100, Denmark
Aalborg Universitetshospital
Aalborg, North Denmark, 9000, Denmark
F345 H.C. Andersen's Children's Hospital
Odense, Region Syddanmark, 5000, Denmark
Odense Universitetshospital
Odense, Region Syddanmark, 5000, Denmark
University Clinic Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Universitätsklinikum Augsburg
Augsburg, Bavaria, 86156, Germany
University Clinic Regensburg
Regensburg, Bavaria, 93053, Germany
Klinikum der Johann-Wolfgang Goethe-Universitat
Frankfurt am Main, Hesse, 60528, Germany
Universitätsklinikum Bonn
Bonn, North Rhine-Westphalia, 53127, Germany
Uniklinik Köln
Cologne, North Rhine-Westphalia, 50937, Germany
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, 45147, Germany
Vivantes Klinikum Neukölln
Berlin, 12351, Germany
Klinikum Mannheim Universitätsklinikum gGmbH
Manheim, 68167, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
Queen Mary Hospital
Hong Kong, 999077, Hong Kong
Sheba Medical Center
Ramat Gan, Tel Aviv, 5262100, Israel
Soroka University Medical Centre
Beersheba, 50937, Israel
Rambam Medical Center
Haifa, 31096, Israel
Hadassah Ein Kerem Medical Center
Jerusalem, 91120, Israel
Rabin Medical Center
Petah Tikva, 49372, Israel
Schneider Children's Medical Center of Israel
Petah Tikvah, 4920235, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
Ospedale Bellaria
Bologna, Emilia-Romagna, 40139, Italy
Istituto Nazionale Tumori Regina Elena
Rome, Lazio, 00144, Italy
Ospedale San Raffaele S.r.l.
Milan, Lombardy, 20132, Italy
Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
Milan, Lombardy, 20133, Italy
Istituto Clinico Humanitas
Rozzano, Lombardy, 20089, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Turin, Piedmont, 10126, Italy
Istituto Oncologico Veneto
Padova, Veneto, 35128, Italy
National Cancer Center Hospital
Chūō, 104-0045, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, 812-8582, Japan
Kyoto University Hospital
Kyoto, 606-8507, Japan
Osaka City General Hospital
Osaka, 534-0021, Japan
Hokkaido University Hospital
Sapporo, 060-8648, Japan
The University of Tokyo Hospital
Tokyo, Japan
Erasmus MC
Rotterdam, South Holland, 3015 GD, Netherlands
Universitair Medisch Centrum Utrecht Cancer Center
Utrecht, 3584 CX, Netherlands
KK Women's and Children's Hospital
Singapore, 229899, Singapore
National Cancer Centre
Singapore, 308433, Singapore
National Neuroscience Institute
Singapore, 308433, Singapore
CHA Bundang Medical Center
Bundang-Gu, Seongnam-Si, Gyeonggido, 13496, South Korea
Seoul National University Bundang Hospital
Bundang-gu, Seongnam-si, Gyeonggido, 13620, South Korea
Seoul National University Hospital
Bundang-gu, Seongnam-si, Gyeonggido, 13620, South Korea
National Cancer Center
Ilsandong-Gu, Goyang-Si, Gyeonggido, 10408, South Korea
Gangnam Severance Hospital, Yonsei University Health System
Gangnam, Seoul Teugbyeolsi, 06273, South Korea
Samsung Medical Center
Gangnam-Gu, Seoul Teugbyeolsi, 06351, South Korea
Seoul National University Hospital
Jongno-Gu, Seoul Teugbyeolsi, 03080, South Korea
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 5505, South Korea
Severance Hospital Yonsei University Health System
Seoul, 03722, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 6591, South Korea
Hospital Sant Joan de Deu
Esplugues de Llobregat, Barcelona, 8950, Spain
Clinica Universidad Navarra
Pamplona, Navarre, 31008, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 8035, Spain
Hospital Infantil Universitario Niño Jesus
Madrid, 28009, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario HM Sanchinarro
Madrid, 28050, Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico
Salamanca, 37007, Spain
Hospital Universitari i Politecnic La Fe de Valencia - Adults
Valencia, 46026, Spain
Hospital Universitari i Politecnic La Fe de Valencia - Pediatrics
Valencia, 46026, Spain
Centre Hospitalier Universitaire Vaudois
Lausanne, Canton of Vaud, 1011, Switzerland
Universitätsspital Zürich
Zurich, 8091, Switzerland
Addenbrooke's Hospital
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Lanarkshire, G12 0YN, United Kingdom
Royal Hospital for Children (Glasgow)
Glasgow, Lanarkshire, G51 4TF, United Kingdom
Clatterbridge Cancer Centre - Liverpool
Liverpool, Lancashire, L7 8YA, United Kingdom
The Christie NHS Foundation Trust
Manchester, Lancashire, M20 4BX, United Kingdom
The Royal Marsden in Sutton, Surrey
Sutton, Surrey, SM2 5PT, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom
Freeman Hospital
Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom
St James University Hospital
Leeds, West Yorkshire, LS9 7TF, United Kingdom
The Leeds Teaching Hospitals NHS Trust, Leeds General Infimary
Leeds, LS1 3EX, United Kingdom
Guy's Hospital
London, SE19RT, United Kingdom
Churchill Hospital
Oxford, Ox3 7LE, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
September 27, 2022
First Posted
October 14, 2022
Study Start
January 23, 2023
Primary Completion (Estimated)
June 1, 2028
Study Completion (Estimated)
June 1, 2028
Last Updated
April 16, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com