ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION)

April 13, 2026 updated by: Jazz Pharmaceuticals

ONC201 for the Treatment of Newly Diagnosed H3 K27M-mutant Diffuse Glioma Following Completion of Radiotherapy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

510

Phase

  • Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1426ABP
        • Recruiting
        • FLENI Neurologia
        • Contact:
        • Principal Investigator:
          • Agustin Maximo Cardoso, MD
  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Sydney Children's Hospital
        • Contact:
        • Principal Investigator:
          • David Ziegler, BS, MB, MD
      • Sydney, New South Wales, Australia, 2065
    • Queensland
      • Herston, Queensland, Australia
        • Recruiting
        • Royal Brisbane and Women's Hospital
        • Contact:
        • Principal Investigator:
          • Zarnie Lwin, MD
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Olivia Newton-John Cancer Research Institute (ONJCRI)
        • Contact:
        • Principal Investigator:
          • Lawrence Cher
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
  • Austria
    • State of Vienna
      • Vienna, State of Vienna, Austria, 01090
        • Recruiting
        • Medical University of Vienna - Adults
        • Contact:
        • Principal Investigator:
          • Anna Bergmeister-Berghoff, MD
      • Vienna, State of Vienna, Austria
        • Recruiting
        • Medical University of Vienna - Pediatrics
        • Contact:
        • Principal Investigator:
          • Johannes Gojo
  • Brazil
      • São Paulo, Brazil
        • Recruiting
        • Instituto do Cancer do Estado de Sao Paulo
        • Contact:
        • Principal Investigator:
          • Olavo Feher, MD
      • São Paulo, Brazil, 04023-062
        • Recruiting
        • Hospital do GRAACC
        • Contact:
        • Principal Investigator:
          • Andrea Maria Cappellano
      • São Paulo, Brazil
        • Recruiting
        • Hcor Research Institute
        • Contact:
        • Principal Investigator:
          • Gabriel Batistella
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Recruiting
        • Tom Baker Cancer Cetre
        • Contact:
        • Principal Investigator:
          • Paula De Robles, MD
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Recruiting
        • BC Cancer - The Vancouver Center
        • Principal Investigator:
          • Rebecca Harrison, MD
        • Contact:
          • Rebecca Harrison, MD
          • Phone Number: +1-604-877-6000
      • Vancouver, British Columbia, Canada, V6H 0B3
        • Recruiting
        • Children's & Women's Health Care of BC
        • Contact:
        • Principal Investigator:
          • George Michaiel
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • Recruiting
        • London Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Seth Climans, MD
      • Ottawa, Ontario, Canada, K1H 8L1
        • Recruiting
        • Childrens Hospital of Eastern Ontario
        • Contact:
        • Principal Investigator:
          • Donna Johnston, MD
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Mary Lim-Fat, MD
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • Princess Margaret Hospital
        • Contact:
        • Principal Investigator:
          • Julie Bennett, MD
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
  • Denmark
    • Capital
      • Copenhagen, Capital, Denmark, 2100
        • Recruiting
        • Copenhagen University Hospital
        • Contact:
        • Principal Investigator:
          • Søren Møller, MD
    • North Denmark
      • Aalborg, North Denmark, Denmark, 9000
        • Recruiting
        • Aalborg Universitetshospital
        • Contact:
          • Charlotte Aaquist Haslund, MD
          • Email: cah@rn.dk
        • Principal Investigator:
          • Charlotte Aaquist Haslund, MD
    • Region Syddanmark
      • Odense, Region Syddanmark, Denmark, 5000
        • Recruiting
        • F345 H.C. Andersen's Children's Hospital
        • Contact:
        • Principal Investigator:
          • Michael Callesen
      • Odense, Region Syddanmark, Denmark, 5000
        • Recruiting
        • Odense Universitetshospital
        • Contact:
        • Principal Investigator:
          • Rikke Dahlrot, MD
  • Germany
      • Berlin, Germany, 12351
        • Recruiting
        • Vivantes Klinikum Neukölln
        • Contact:
        • Principal Investigator:
          • Andreas Jödicke, MD
      • Manheim, Germany, 68167
        • Recruiting
        • Klinikum Mannheim Universitätsklinikum gGmbH
        • Contact:
        • Principal Investigator:
          • Lukas Bunse, MD
      • Tübingen, Germany, 72076
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
    • Bavaria
      • Augsburg, Bavaria, Germany, 86156
      • Regensburg, Bavaria, Germany, 93053
        • Recruiting
        • University Clinic Regensburg
        • Principal Investigator:
          • Peter Hau, MD
        • Contact:
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 60528
        • Recruiting
        • Klinikum der Johann-Wolfgang Goethe-Universitat
        • Principal Investigator:
          • Michael Ronellenfitsch, MD
        • Contact:
    • North Rhine-Westphalia
      • Bonn, North Rhine-Westphalia, Germany, 53127
      • Cologne, North Rhine-Westphalia, Germany, 50937
        • Recruiting
        • Uniklinik Koln
        • Contact:
        • Principal Investigator:
          • Roland Goldbrunner, MD, PhD
      • Essen, North Rhine-Westphalia, Germany, 45147
        • Recruiting
        • Universitatsklinikum Essen
        • Contact:
        • Principal Investigator:
          • Sied Kebir
  • Hong Kong
      • Hong Kong, Hong Kong, 999077
        • Recruiting
        • Queen Mary Hospital
        • Contact:
        • Principal Investigator:
          • Aya El Helali, MD
  • Israel
      • Beersheba, Israel, 50937
        • Recruiting
        • Soroka University Medical Centre
        • Contact:
        • Principal Investigator:
          • Abed El Salem Abu Quider, MD
      • Haifa, Israel, 31096
      • Jerusalem, Israel, 91120
        • Recruiting
        • Hadassah Ein Kerem Medical Center
        • Contact:
        • Principal Investigator:
          • Alexander Lossos, MD
      • Petah Tikva, Israel, 49372
        • Recruiting
        • Rabin Medical Center
        • Principal Investigator:
          • Shlomit Yust-Katz, MD
        • Contact:
      • Petah Tikvah, Israel, 4920235
        • Recruiting
        • Schneider Children's Medical Center of Israel
        • Contact:
        • Principal Investigator:
          • Helen Toledano, MD
      • Tel Aviv, Israel, 64239
        • Recruiting
        • Tel Aviv Sourasky Medical Center
        • Contact:
        • Principal Investigator:
          • Deborah Blumenthal, MD
    • Tel Aviv
      • Ramat Gan, Tel Aviv, Israel, 5262100
  • Italy
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40139
        • Recruiting
        • Ospedale Bellaria
        • Principal Investigator:
          • Enrico Franceschi, MD
        • Contact:
    • Lazio
      • Rome, Lazio, Italy, 00144
        • Withdrawn
        • Istituto Nazionale Tumori Regina Elena
    • Lombardy
      • Milan, Lombardy, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele S.r.l.
        • Principal Investigator:
          • Gaetano Finocchiaro, MD
        • Contact:
      • Milan, Lombardy, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
        • Contact:
        • Principal Investigator:
          • Paola Gaviani, MD
      • Rozzano, Lombardy, Italy, 20089
        • Recruiting
        • Istituto Clinico Humanitas
        • Contact:
        • Principal Investigator:
          • Matteo Simonelli, MD
    • Piedmont
      • Turin, Piedmont, Italy, 10126
        • Recruiting
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
        • Principal Investigator:
          • Alessia Pellerino, MD
        • Contact:
    • Veneto
      • Padova, Veneto, Italy, 35128
        • Recruiting
        • Istituto Oncologico Veneto
        • Contact:
        • Principal Investigator:
          • Giuseppe Lombardi, MD, PhD
  • Japan
      • Chūō, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Contact:
        • Principal Investigator:
          • Yoshitaka Narita, MD
      • Fukuoka, Japan, 812-8582
        • Recruiting
        • National Hospital Organization Kyushu Cancer Center
        • Principal Investigator:
          • Yuhki Koga
        • Contact:
      • Kyoto, Japan, 606-8507
        • Recruiting
        • Kyoto University Hospital
        • Contact:
        • Principal Investigator:
          • Yoshi Arakawa, MD
      • Osaka, Japan, 534-0021
      • Sapporo, Japan, 060-8648
        • Recruiting
        • Hokkaido University Hospital
        • Contact:
        • Principal Investigator:
          • Atsushi Manabe
      • Tokyo, Japan
        • Recruiting
        • The University of Tokyo Hospital
        • Contact:
        • Principal Investigator:
          • hirokazu Takami, MD
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Recruiting
        • Universitair Medisch Centrum Utrecht Cancer Center
        • Contact:
        • Principal Investigator:
          • Tom J Snijders
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 GD
        • Recruiting
        • Erasmus MC
        • Contact:
        • Principal Investigator:
          • Jacoline Bromberg
  • Singapore
      • Singapore, Singapore, 229899
        • Recruiting
        • KK Women's and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Enrica Tan Ee Kar, MBBS
      • Singapore, Singapore, 308433
      • Singapore, Singapore, 308433
  • South Korea
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital Yonsei University Health System
        • Contact:
        • Principal Investigator:
          • Jong Hee Chang, MD, PhD
      • Seoul, South Korea, 6591
        • Recruiting
        • The Catholic University of Korea, Seoul St. Mary's Hospital
        • Contact:
        • Principal Investigator:
          • Jae-Sung Park, MD
    • Gyeonggido
      • Bundang-Gu, Seongnam-Si, Gyeonggido, South Korea, 13496
        • Recruiting
        • CHA Bundang Medical Center
        • Contact:
        • Principal Investigator:
          • Kyung Gi Cho
      • Bundang-gu, Seongnam-si, Gyeonggido, South Korea, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
        • Principal Investigator:
          • Chae-Yong Kim, MD
      • Bundang-gu, Seongnam-si, Gyeonggido, South Korea, 13620
        • Recruiting
        • Seoul National University Hospital
        • Principal Investigator:
          • Tae Min Kim
        • Contact:
      • Ilsandong-Gu, Goyang-Si, Gyeonggido, South Korea, 10408
        • Recruiting
        • National Cancer Center
        • Contact:
        • Principal Investigator:
          • Heon Yoo, MD, PhD
    • Seoul Teugbyeolsi
      • Gangnam, Seoul Teugbyeolsi, South Korea, 06273
        • Recruiting
        • Gangnam Severance Hospital, Yonsei University Health System
        • Contact:
        • Principal Investigator:
          • Jun Won Kim, MD, PhD
      • Gangnam-Gu, Seoul Teugbyeolsi, South Korea, 06351
        • Recruiting
        • Samsung Medical Center
        • Contact:
        • Principal Investigator:
          • Ji Won Lee, MD, PhD
      • Jongno-Gu, Seoul Teugbyeolsi, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
        • Principal Investigator:
          • Hyoung Jin Kang, MD
      • Seoul, Seoul Teugbyeolsi, South Korea, 5505
        • Recruiting
        • Asan Medical Center
        • Principal Investigator:
          • Hyungwoo Cho
        • Contact:
  • Spain
      • Barcelona, Spain, 8035
        • Recruiting
        • Hospital Universitario Vall d'Hebron
        • Contact:
        • Principal Investigator:
          • Maria Vieito Villar, MD, MSc
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clinic de Barcelona
        • Principal Investigator:
          • Estela Pineda, MD
        • Contact:
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
        • Principal Investigator:
          • Juan Manuel Sepulveda Sánchez, MD
      • Madrid, Spain, 28009
        • Recruiting
        • Hospital Infantil Universitario Niño Jesús
        • Contact:
        • Principal Investigator:
          • Alvaro Lassaletta, MD
      • Madrid, Spain, 28050
        • Recruiting
        • Hospital Universitario HM Sanchinarro
        • Contact:
        • Principal Investigator:
          • Angela Santiago
      • Salamanca, Spain, 37007
        • Recruiting
        • Complejo Asistencial Universitario de Salamanca - H. Clinico
        • Contact:
        • Principal Investigator:
          • Miguel Navarro Martin, MD
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politecnic La Fe de Valencia - Adults
        • Contact:
        • Principal Investigator:
          • Regina Gironés Sarrió, MD
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politecnic La Fe de Valencia - Pediatrics
        • Contact:
        • Principal Investigator:
          • Antonio Juan Ribelles, MD
    • Barcelona
      • Esplugues de Llobregat, Barcelona, Spain, 8950
        • Recruiting
        • Hospital Sant Joan de Déu
        • Contact:
        • Principal Investigator:
          • Miriam Pavon Mengual, MD
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Clinica Universidad Navarra
        • Contact:
        • Principal Investigator:
          • Jaime Gallego Perez de Larraya, MD
  • Switzerland
      • Zurich, Switzerland, 8091
        • Recruiting
        • Universitatsspital Zurich
        • Contact:
        • Principal Investigator:
          • Emilie Le Rhun, MD, PhD
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Switzerland, 1011
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois
        • Contact:
        • Principal Investigator:
          • Andreas Hottinger, MD, PhD
  • United Kingdom
      • Leeds, United Kingdom, LS1 3EX
        • Recruiting
        • The Leeds Teaching Hospitals NHS Trust, Leeds General Infimary
        • Contact:
        • Principal Investigator:
          • Simone Wilkins, MD
      • London, United Kingdom, SE19RT
        • Recruiting
        • Guy's Hospital
        • Contact:
        • Principal Investigator:
          • Lucy Brazil, MD
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Churchill Hospital
        • Contact:
        • Principal Investigator:
          • Meera Nandhabalan, MD
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrooke's Hospital
        • Contact:
        • Principal Investigator:
          • Fiona Harris, MBBS, MD
    • Lanarkshire
      • Glasgow, Lanarkshire, United Kingdom, G12 0YN
        • Recruiting
        • Beatson West Of Scotland Cancer Centre
        • Contact:
        • Principal Investigator:
          • Stefan Nowicki, MD, PhD
      • Glasgow, Lanarkshire, United Kingdom, G51 4TF
        • Recruiting
        • Royal Hospital for Children (Glasgow)
        • Contact:
        • Principal Investigator:
          • Jairam Sastry, MD
    • Lancashire
      • Liverpool, Lancashire, United Kingdom, L7 8YA
        • Recruiting
        • Clatterbridge Cancer Centre - Liverpool
        • Contact:
        • Principal Investigator:
          • Shaveta Mehta, MD, PhD
      • Manchester, Lancashire, United Kingdom, M20 4BX
        • Recruiting
        • The Christie Nhs Foundation Trust
        • Contact:
        • Principal Investigator:
          • Catherine McBain, MD
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Recruiting
        • The Royal Marsden in Sutton, Surrey
        • Contact:
        • Principal Investigator:
          • Fernando Carceller, MD
    • Tyne and Wear
      • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
        • Recruiting
        • Freeman Hospital
        • Contact:
        • Principal Investigator:
          • Joanne Lewis, MRCPCH
      • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP
        • Recruiting
        • Royal Victoria Infirmary
        • Contact:
        • Principal Investigator:
          • Joanne Lewis, MRCPCH
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS9 7TF
        • Recruiting
        • St James University Hospital
        • Principal Investigator:
          • Fiona Collinson
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Completed
        • Phoenix Childrens Hospital
      • Phoenix, Arizona, United States, 85013
        • Active, not recruiting
        • Barrow Neurological Institute
      • Phoenix, Arizona, United States, 85054
        • Completed
        • Mayo Clinic Arizona
      • Phoenix, Arizona, United States, 85006
        • Completed
        • Banner MD Anderson Cancer Center
    • California
      • La Jolla, California, United States, 92093
        • Active, not recruiting
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90027
        • Completed
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles, California, United States, 90095
        • Completed
        • UCLA University of California Los Angeles
      • Orange, California, United States, 92868
        • Active, not recruiting
        • University of California Irvine
      • Orange, California, United States, 92868
        • Completed
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94143
        • Active, not recruiting
        • University of California San Francisco
      • San Francisco, California, United States, 94143
        • Active, not recruiting
        • UCSF Benioff Children's Hospital
      • Santa Monica, California, United States, 90404
        • Active, not recruiting
        • Providence Saint John's Cancer Institute
      • Stanford, California, United States, 94350
        • Completed
        • Stanford Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Active, not recruiting
        • Yale University
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Completed
        • MedStar Georgetown University Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Active, not recruiting
        • Mayo Clinic Jacksonville
      • Miami, Florida, United States, 33176
        • Active, not recruiting
        • Miami Cancer Institute
      • Tampa, Florida, United States, 33612
        • Active, not recruiting
        • Moffitt Cancer Center
      • Tampa, Florida, United States, 33607
        • Completed
        • St Joseph's Children's Hospital of Tampa
      • Weston, Florida, United States, 33331
        • Completed
        • Cleveland Clinic Florida
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Completed
        • Children's Healthcare of Atlanta
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Completed
        • Kapi'olani Medical Center for Women and Children
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Active, not recruiting
        • Feinberg School of Medicine Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Active, not recruiting
        • Indiana University School of Medicine - Indianapolis
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Active, not recruiting
        • University of Iowa Hospitals & Clinics
    • Kentucky
      • Louisville, Kentucky, United States, 40241
        • Active, not recruiting
        • Norton Healthcare
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Completed
        • Ochsner Medical Center - New Orleans
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Completed
        • University of Maryland School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Active, not recruiting
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Active, not recruiting
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Active, not recruiting
        • University of Michigan Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Active, not recruiting
        • University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Active, not recruiting
        • Mayo Clinic - Cancer Center - Rochester
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Active, not recruiting
        • Washington University School of Medicine/St. Louis Children's Hospital
    • Montana
      • Great Falls, Montana, United States, 59405
        • Withdrawn
        • Benefis Hospital Sletten Cancer Institute
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Completed
        • University of Nebraska Medical Center
    • New Jersey
      • Neptune City, New Jersey, United States, 07753
        • Active, not recruiting
        • Jersey Shore University Medical Center
      • Summit, New Jersey, United States, 07901
        • Active, not recruiting
        • Overlook Medical Center
    • New York
      • Albany, New York, United States, 12208
        • Completed
        • Albany Medical Center
      • New York, New York, United States, 10032
        • Active, not recruiting
        • Columbia University Medical Center
      • New York, New York, United States, 10075
        • Completed
        • Lenox Hill Hospital
      • New York, New York, United States, 10029
        • Active, not recruiting
        • Montefiore Medical Park
      • New York, New York, United States, 10032-3726
        • Active, not recruiting
        • Laura & Isaac Perlmutter Cancer Center - NYU ACC
      • New York, New York, United States, 10029
        • Completed
        • Children's Hospital at Montefiore Medical Center
      • Rochester, New York, United States, 14642
        • Completed
        • University of Rochester Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Active, not recruiting
        • Levine Cancer Institute/ Atrium Health
      • Durham, North Carolina, United States, 27710
        • Active, not recruiting
        • Duke Cancer Institute
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Active, not recruiting
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Active, not recruiting
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43210
        • Active, not recruiting
        • Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Active, not recruiting
        • University of Oklahoma Peggy and Charles Stephenson Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Active, not recruiting
        • Providence Health and Services St. Vincent Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Active, not recruiting
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Active, not recruiting
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15232
        • Completed
        • UPMC Hillman Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • Completed
        • UPMC Children's Hospital of Pittsburgh
    • Texas
      • Austin, Texas, United States, 78723
        • Completed
        • Dell Children's Medical Center of Central Texas
      • Dallas, Texas, United States, 75390
        • Active, not recruiting
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75246
        • Active, not recruiting
        • Neuro-Oncology Associates
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • University of Texas MD Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Completed
        • UT Health Houston Neurosciences - Texas Medical Center
      • San Antonio, Texas, United States, 78229
        • Active, not recruiting
        • University of Texas - San Antonio - Health Science Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Active, not recruiting
        • University of Utah - Huntsman Cancer Institute
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Active, not recruiting
        • Inova Schar Cancer Institute
      • Norfolk, Virginia, United States, 23507
        • Completed
        • Children's Hospital of The King's Daughter
    • Washington
      • Seattle, Washington, United States, 98195
        • Active, not recruiting
        • University of Washington
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Active, not recruiting
        • University of Wisconsin - Madison

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Group
Other: Placebo
Participants will receive placebo (same number of capsules as the dordaviprone dose) on dosing days
Experimental: Dordaviprone Twice Weekly Group
Drug: Dordaviprone (ONC201)
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.
Experimental: Dordaviprone Once Weekly Group
Drug: Dordaviprone (ONC201) + Placebo
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: From date of randomization until date of death from any cause, assessed up to approximately 44 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: From date of randomization up to 44 months
Incidence of overall, treatment-related, Grade 3 or higher in severity, serious, fatal, those resulting in treatment discontinuation, and events of special interest
From date of randomization up to 44 months
Change from baseline in clinical laboratory parameters
Time Frame: From date of randomization up to 44 months
Percentage of participants with clinically significant laboratory results
From date of randomization up to 44 months
Corticosteroid response
Time Frame: From date of randomization up to 44 months
Corticosteroid response will be measured by a confirmed 50% decrease in use of dexamethasone or equivalent
From date of randomization up to 44 months
Progression Free Survival (PFS) using RANO 2.0 Criteria for All Participants
Time Frame: From date of randomization until the date of first documented progression assessed up to approximately 44 months.
PFS is defined as time from randomization to disease progression (PD) or death.
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
Time Frame: From date of randomization up to 44 months
PFS is defined as time from randomization to disease progression (PD) or death.
From date of randomization up to 44 months
Distribution of Graded Clinical Laboratory Parameter
Time Frame: From date of randomization up to 44 months
Breakdown of how many participants fall into each severity grade. Grade 1 for mild up to Grade 4 for severe or life threatening.
From date of randomization up to 44 months
Time to First Corticosteroid Response
Time Frame: From date of randomization up to 44 months
Time from the first dose to the nominal analysis timepoint when the response criteria are first met.
From date of randomization up to 44 months
Duration of First Corticosteroid Response
Time Frame: From date of randomization up to 44 months
Time from first response to end of first response.
From date of randomization up to 44 months
Cumulative Duration of Corticosteroid Responses
Time Frame: From date of randomization up to 44 months
Total durations of response, irrespective of censoring, to account for participants with multiple responses during the study.
From date of randomization up to 44 months
Corticosteroid Dose and Change from Baseline Over Time
Time Frame: From date of randomization up to 44 months
From date of randomization up to 44 months
Time to Corticosteroid Use Deterioration
Time Frame: From date of randomization up to 44 months
Time from first dose of study intervention to time when corticosteroid daily dose ≥ baseline daily dose + 2 mg at 2 consecutive analysis time points or death.
From date of randomization up to 44 months
Performance status response
Time Frame: From date of randomization up to 44 months
Performance status response will be measured by confirmed increase in Karnofsky Performance Status (KPS) or Lansky Performance Status (LPS).
From date of randomization up to 44 months
Time to first performance status response
Time Frame: From date of randomization up to 44 months
time from the first dose of study intervention to the nominal analysis timepoint when the response criteria are first met.
From date of randomization up to 44 months
Duration of first performance status response
Time Frame: From date of randomization up to 44 months
Time from response to end of response.
From date of randomization up to 44 months
Cumulative duration of performance status responses
Time Frame: From date of randomization up to 44 months
Total durations of response, irrespective of censoring, to account for patients with multiple responses during the study
From date of randomization up to 44 months
Performance status and change from baseline over time
Time Frame: From date of randomization up to 44 months
From date of randomization up to 44 months
Time to performance status deterioration
Time Frame: From date of randomization up to 44 months
As time from the first dose of study intervention to time when KPS/LPS score < baseline or death.
From date of randomization up to 44 months
Change from Baseline in European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30)
Time Frame: Day 1 (pre-dose), up to 44 months
The EORTC QLQ-C30 will be administered to participants ≥ 18 years. It evaluates the following scales: functional, symptom, global health, quality of life, and financial impact.
Day 1 (pre-dose), up to 44 months
Change from Baseline in Quality of Life-Core Questionnaire Brain Module (QLQ-BN20)
Time Frame: Day 1 (pre-dose), up to 44 months
The QLQ-bN20 will be administered to participants ≥ 18 years of age and will measure health related quality of life.
Day 1 (pre-dose), up to 44 months
Change from Baseline in MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT)
Time Frame: Day 1 (pre-dose), up to 44 months
The MDASI-BT will be administered to participants ≥ 18 years of age. It is a 22-item assessment that measures brain tumor related symptoms and impact on daily function. It will assess six areas on a scale of 0-10 (10 indicating worse or more severe symptoms): affective, cognitive, focal neurologic deficit, constitutional, generalized symptom, and gastrointestinal.
Day 1 (pre-dose), up to 44 months
Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module
Time Frame: Day 1 (pre-dose), up to 44 months
The PedsQL will be administered to participants 2 to < 18 years of age. It measures 4 scales: physical, emotional, social, and school functioning.
Day 1 (pre-dose), up to 44 months
Change from Baseline in Neurologic Assessment in Neuro-Oncology (NANO) Score
Time Frame: Day 1 (pre-dose), up to 44 months
The NANO score evaluates gait, strength, ataxia in the upper extremity, sensation, visual field, facial strength, language, level of consciousness, and behavior.
Day 1 (pre-dose), up to 44 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jazz Pharmaceuticals

Collaborators

Chimerix, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2023

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

September 27, 2022

First Submitted That Met QC Criteria

October 12, 2022

First Posted (Actual)

October 14, 2022

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONC201-108

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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