AzTrials
AzTrials

H3 K27MPhase 3ACTIONNCT05580562

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

A Phase 3 study testing Dordaviprone (ONC201) in people with H3 K27M and Glioma, run by Jazz Pharmaceuticals at 162 sites in 18 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Any age
Conditions the study is for
H3 K27M, Glioma
What is being tested?
Dordaviprone (ONC201)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
510 participants
Where
162 sitesin 18 countries
Study dates
23 Jan 2023to Jun 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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).

Who cannot join

  • 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.
Show all 26Show fewer
  • 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.
  • Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks.
  • Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization:
  • Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L.
  • 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).
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.
  • Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate < 60 mL/min/1.73 m2).
  • QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening.
  • Known hypersensitivity to any excipients used in the study intervention formulation.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

162 sites in 18 countries. Contact the study team or a site near you to ask about taking part.

Clinical Trial Disclosure & Transparency contact

215-832-3750

ClinicalTrialDisclosure@jazzpharma.com

162 sites in 18 countries

United States67 sites

  • Albany Medical Center

    Albany, New York, 12208

    Completed

  • University of Michigan Hospital

    Ann Arbor, Michigan, 48109

    Active, not recruiting

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30342

    Completed

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

    Completed

  • University of Maryland School of Medicine

    Baltimore, Maryland, 21201

    Completed

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

    Active, not recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Active, not recruiting

  • Levine Cancer Institute/ Atrium Health

    Charlotte, North Carolina, 28204

    Active, not recruiting

  • Feinberg School of Medicine Northwestern University

    Chicago, Illinois, 60611

    Active, not recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

    Active, not recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Active, not recruiting

  • Ohio State University

    Columbus, Ohio, 43210

    Active, not recruiting

  • Neuro-Oncology Associates

    Dallas, Texas, 75246

    Active, not recruiting

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

    Active, not recruiting

  • Duke Cancer Institute

    Durham, North Carolina, 27710

    Active, not recruiting

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

    Active, not recruiting

  • Benefis Hospital Sletten Cancer Institute

    Great Falls, Montana, 59405

    Withdrawn

  • Kapi'olani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

    Completed

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Active, not recruiting

  • UT Health Houston Neurosciences - Texas Medical Center

    Houston, Texas, 77030

    Completed

  • Indiana University School of Medicine - Indianapolis

    Indianapolis, Indiana, 46202

    Active, not recruiting

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

    Active, not recruiting

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

    Active, not recruiting

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

    Active, not recruiting

  • Kaiser Permanente Los Angeles Medical Center

    Los Angeles, California, 90027

    Completed

  • UCLA University of California Los Angeles

    Los Angeles, California, 90095

    Completed

  • Norton Healthcare

    Louisville, Kentucky, 40241

    Active, not recruiting

  • University Of Wisconsin - Madison

    Madison, Wisconsin, 53792

    Active, not recruiting

  • Miami Cancer Institute

    Miami, Florida, 33176

    Active, not recruiting

  • University of Minnesota

    Minneapolis, Minnesota, 55455

    Active, not recruiting

  • Jersey Shore University Medical Center

    Neptune City, New Jersey, 07753

    Active, not recruiting

  • Yale University

    New Haven, Connecticut, 06511

    Active, not recruiting

  • Ochsner Medical Center - New Orleans

    New Orleans, Louisiana, 70121

    Completed

  • Children's Hospital at Montefiore Medical Center

    New York, New York, 10029

    Completed

  • Montefiore Medical Park

    New York, New York, 10029

    Active, not recruiting

  • Laura & Isaac Perlmutter Cancer Center - NYU ACC

    New York, New York, 10032-3726

    Active, not recruiting

  • Columbia University Medical Center

    New York, New York, 10032

    Active, not recruiting

  • Lenox Hill Hospital

    New York, New York, 10075

    Completed

  • Children's Hospital of The King's Daughter

    Norfolk, Virginia, 23507

    Completed

  • University of Oklahoma Peggy and Charles Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

    Active, not recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68114

    Completed

  • Children's Hospital of Orange County

    Orange, California, 92868

    Completed

  • University of California Irvine

    Orange, California, 92868

    Active, not recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Active, not recruiting

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

    Active, not recruiting

  • Banner MD Anderson Cancer Center

    Phoenix, Arizona, 85006

    Completed

  • Barrow Neurological Institute

    Phoenix, Arizona, 85013

    Active, not recruiting

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

    Completed

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

    Completed

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

    Completed

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Completed

  • Providence Health and Services St. Vincent Medical Center

    Portland, Oregon, 97239

    Active, not recruiting

  • Mayo Clinic - Cancer Center - Rochester

    Rochester, Minnesota, 55905

    Active, not recruiting

  • University of Rochester Medical Center

    Rochester, New York, 14642

    Completed

  • University of Utah - Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

    Active, not recruiting

  • University of Texas - San Antonio - Health Science Center

    San Antonio, Texas, 78229

    Active, not recruiting

  • UCSF Benioff Children's Hospital

    San Francisco, California, 94143

    Active, not recruiting

  • University of California San Francisco

    San Francisco, California, 94143

    Active, not recruiting

  • Providence Saint John's Cancer Institute

    Santa Monica, California, 90404

    Active, not recruiting

  • University of Washington

    Seattle, Washington, 98195

    Active, not recruiting

  • Washington University School of Medicine/St. Louis Children's Hospital

    St Louis, Missouri, 63110

    Active, not recruiting

  • Stanford Cancer Center

    Stanford, California, 94350

    Completed

  • Overlook Medical Center

    Summit, New Jersey, 07901

    Active, not recruiting

  • St Joseph's Children's Hospital of Tampa

    Tampa, Florida, 33607

    Completed

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Active, not recruiting

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

    Completed

  • Cleveland Clinic Florida

    Weston, Florida, 33331

    Completed

Other trials in United States

United Kingdom12 sites, 12 recruiting

  • Addenbrooke's Hospital

    Cambridge, Cambridgeshire, CB2 0QQ

    Fiona Harris, MBBS, MD, f.harris3@nhs.net

    Fiona Harris, MBBS, MD

    Recruiting

  • Beatson West of Scotland Cancer Centre

    Glasgow, Lanarkshire, G12 0YN

    Stefan Nowicki, MD, PhD, stefan.nowicki@ggc.scot.nhs.uk

    Stefan Nowicki, MD, PhD

    Recruiting

  • Royal Hospital for Children (Glasgow)

    Glasgow, Lanarkshire, G51 4TF

    Jairam Sastry, MD, jairam.sastry@ggc.scot.nhs.uk

    Jairam Sastry, MD

    Recruiting

  • St James University Hospital

    Leeds, West Yorkshire, LS9 7TF

    Fiona Collinson, fiona.collinson@nhs.net

    Fiona Collinson

    Recruiting

  • The Leeds Teaching Hospitals NHS Trust, Leeds General Infimary

    Leeds, LS1 3EX

    Simone Wilkins, MD, simonewilkins@nhs.net

    Simone Wilkins, MD

    Recruiting

  • Clatterbridge Cancer Centre - Liverpool

    Liverpool, Lancashire, L7 8YA

    Shaveta Mehta, MD, PhD, shaveta.mehta1@nhs.net

    Shaveta Mehta, MD, PhD

    Recruiting

  • Guy's Hospital

    London, SE19RT

    Lucy Brazil, MD, Lucy.Brazil@gstt.nhs.uk

    Lucy Brazil, MD

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester, Lancashire, M20 4BX

    Catherine McBain, MD, catherine.mcbain1@nhs.net

    Catherine McBain, MD

    Recruiting

  • Royal Victoria Infirmary

    Newcastle upon Tyne, Tyne and Wear, NE1 4LP

    Joanne Lewis, MRCPCH, joanne.lewis@nhs.net

    Joanne Lewis, MRCPCH

    Recruiting

  • Freeman Hospital

    Newcastle upon Tyne, Tyne and Wear, NE7 7DN

    Joanne Lewis, MRCPCH, joanne.lewis@nhs.net

    Joanne Lewis, MRCPCH

    Recruiting

  • Churchill Hospital

    Oxford, Ox3 7LE

    Meera Nandhabalan, MD, meera.nandhabalan@ouh.nhs.uk

    Meera Nandhabalan, MD

    Recruiting

  • The Royal Marsden in Sutton, Surrey

    Sutton, Surrey, SM2 5PT

    Fernando Carceller, MD, fernando.carceller@rmh.nhs.uk

    Fernando Carceller, MD

    Recruiting

Other trials in United Kingdom

Germany11 sites, 11 recruiting

  • Universitätsklinikum Augsburg

    Augsburg, Bavaria, 86156

    Michael Frühwald, MD, michael.fruehwald@klinikum-augsburg.de

    Michael Frühwald, MD

    Recruiting

  • Vivantes Klinikum Neukölln

    Berlin, 12351

    Andreas Jödicke, MD, andreas.joedicke@vivantes.de

    Andreas Jödicke, MD

    Recruiting

  • Universitätsklinikum Bonn

    Bonn, North Rhine-Westphalia, 53127

    Ulrich Herrlinger, MD, ulrich.herrlinger@ukb.uni-bonn.de

    Ulrich Herrlinger, MD

    Recruiting

  • Uniklinik Köln

    Cologne, North Rhine-Westphalia, 50937

    Roland Goldbrunner, MD, PhD, roland.goldbrunner@uk-koeln.de

    Roland Goldbrunner, MD, PhD

    Recruiting

  • Universitätsklinikum Essen

    Essen, North Rhine-Westphalia, 45147

    Sied Kebir, sied.kebir@uk-essen.de

    Sied Kebir

    Recruiting

  • Klinikum der Johann-Wolfgang Goethe-Universitat

    Frankfurt am Main, Hesse, 60528

    Michael Ronellenfitsch, MD, michael.ronellenfitsch@kgu.de

    Michael Ronellenfitsch, MD

    Recruiting

  • University Clinic Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

    Cornelis van Tilburg, MD, PhD, cornelis.vantilburg@kitz-heidelberg.de

    Cornelis van Tilburg, MD, PhD

    Recruiting

  • Universitätsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

    Antje Wick, MD, antje.wick@med.uni-heidelberg.de

    Antje Wick, MD

    Recruiting

  • Klinikum Mannheim Universitätsklinikum gGmbH

    Manheim, 68167

    Lukas Bunse, MD, lukas.bunse@umm.de

    Lukas Bunse, MD

    Recruiting

  • University Clinic Regensburg

    Regensburg, Bavaria, 93053

    Peter Hau, MD, peter.hau@ukr.de

    Peter Hau, MD

    Recruiting

  • Universitätsklinikum Tübingen

    Tübingen, 72076

    Ghazaleh Tabatabai, MD, PhD, ghazaleh.tabatabai@uni-tuebingen.de

    Ghazaleh Tabatabai, MD, PhD

    Recruiting

Other trials in Germany

South Korea10 sites, 10 recruiting

  • Seoul National University Bundang Hospital

    Bundang-gu, Seongnam-si, Gyeonggido, 13620

    Chae-Yong Kim, MD, chaeyong@snu.ac.kr

    Chae-Yong Kim, MD

    Recruiting

  • Seoul National University Hospital

    Bundang-gu, Seongnam-si, Gyeonggido, 13620

    Tae Min Kim, gabriel9@snu.ac.kr

    Tae Min Kim

    Recruiting

  • CHA Bundang Medical Center

    Bundang-Gu, Seongnam-Si, Gyeonggido, 13496

    Kyung Gi Cho, sandori50@chamc.co.kr

    Kyung Gi Cho

    Recruiting

  • Gangnam Severance Hospital, Yonsei University Health System

    Gangnam, Seoul Teugbyeolsi, 06273

    Jun Won Kim, MD, PhD, junwon@yuhs.ac

    Jun Won Kim, MD, PhD

    Recruiting

  • Samsung Medical Center

    Gangnam-Gu, Seoul Teugbyeolsi, 06351

    Ji Won Lee, MD, PhD, leejw.lee@samsung.com

    Ji Won Lee, MD, PhD

    Recruiting

  • National Cancer Center

    Ilsandong-Gu, Goyang-Si, Gyeonggido, 10408

    Heon Yoo, MD, PhD, heonyoo@ncc.re.kr

    Heon Yoo, MD, PhD

    Recruiting

  • Seoul National University Hospital

    Jongno-Gu, Seoul Teugbyeolsi, 03080

    Hyoung Jin Kang, MD, kanghj@snu.ac.kr

    Hyoung Jin Kang, MD

    Recruiting

  • Asan Medical Center

    Seoul, Seoul Teugbyeolsi, 5505

    Hyungwoo Cho, Linker268@gmail.com

    Hyungwoo Cho

    Recruiting

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

    Jong Hee Chang, MD, PhD, changjh@yuhs.ac

    Jong Hee Chang, MD, PhD

    Recruiting

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 6591

    Jae-Sung Park, MD, PhD, jspark82@catholic.ac.kr

    Jae-Sung Park, MD

    Recruiting

Other trials in South Korea

Spain10 sites, 10 recruiting

  • Hospital Clinic de Barcelona

    Barcelona, 08036

    Estela Pineda, MD, epineda@clinic.cat

    Estela Pineda, MD

    Recruiting

  • Hospital Universitario Vall d'Hebron

    Barcelona, 8035

    Maria Vieito Villar, MD, MSc, mvieito@vhio.net

    Maria Vieito Villar, MD, MSc

    Recruiting

  • Hospital Sant Joan de Deu

    Esplugues de Llobregat, Barcelona, 8950

    Miriam Pavon Mengual, MD, miriam.pavon@sjd.es

    Miriam Pavon Mengual, MD

    Recruiting

  • Hospital Infantil Universitario Niño Jesus

    Madrid, 28009

    Alvaro Lassaletta, MD, lassaalvaro@yahoo.com

    Alvaro Lassaletta, MD

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Juan Manuel Sepulveda Sánchez, MD, sepulvedasanchez@seom.org

    Juan Manuel Sepulveda Sánchez, MD

    Recruiting

  • Hospital Universitario HM Sanchinarro

    Madrid, 28050

    Angela Santiago, asantiago@hmhospitales.com

    Angela Santiago

    Recruiting

  • Clinica Universidad Navarra

    Pamplona, Navarre, 31008

    Jaime Gallego Perez de Larraya, MD, jgallego@unav.es

    Jaime Gallego Perez de Larraya, MD

    Recruiting

  • Complejo Asistencial Universitario de Salamanca - H. Clinico

    Salamanca, 37007

    Miguel Navarro Martin, MD, lmnavarro@saludcastillayleon.es

    Miguel Navarro Martin, MD

    Recruiting

  • Hospital Universitari i Politecnic La Fe de Valencia - Adults

    Valencia, 46026

    Regina Gironés Sarrió, MD, girones_reg@gva.es

    Regina Gironés Sarrió, MD

    Recruiting

  • Hospital Universitari i Politecnic La Fe de Valencia - Pediatrics

    Valencia, 46026

    Antonio Juan Ribelles, MD, juan_antrib@gva.es

    Antonio Juan Ribelles, MD

    Recruiting

Other trials in Spain

Canada8 sites, 8 recruiting

  • Tom Baker Cancer Cetre

    Calgary, Alberta, T2N 2T9

    Paula De Robles, MD, paula.derobles@ahs.ca

    Paula De Robles, MD

    Recruiting

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

    Seth Climans, MD, Seth.Climans@lhsc.on.ca

    Seth Climans, MD

    Recruiting

  • Hopital Notre Dame, Lachapelle

    Montreal, Quebec, H2X 3E4

    Sarah Lapointe, sarah.lapointe.med@ssss.gouv.qc.ca

    Sarah Lapointe

    Recruiting

  • Childrens Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

    Donna Johnston, MD, djohnston@cheo.on.ca

    Donna Johnston, MD

    Recruiting

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

    Mary Lim-Fat, MD, maryjane.limfat@sunnybrook.ca

    Mary Lim-Fat, MD

    Recruiting

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 1X8

    Julie Bennett, MD, julie.bennett@sickkids.ca

    Julie Bennett, MD

    Recruiting

  • BC Cancer - The Vancouver Center

    Vancouver, British Columbia, V5Z 4E6

    Rebecca Harrison, MD, +1-604-877-6000

    Rebecca Harrison, MD

    Recruiting

  • Children's & Women's Health Care of BC

    Vancouver, British Columbia, V6H 0B3

    George Michaiel, george.michaiel@cw.bc.ca

    George Michaiel

    Recruiting

Other trials in Canada

Israel7 sites, 7 recruiting

  • Soroka University Medical Centre

    Beersheba, 50937

    Abed El Salem Abu Quider, MD, abeda@clalit.org.il

    Abed El Salem Abu Quider, MD

    Recruiting

  • Rambam Medical Center

    Haifa, 31096

    Tali Siegal, t_siegal@rambam.health.gov.il

    Tali Siegal

    Recruiting

  • Hadassah Ein Kerem Medical Center

    Jerusalem, 91120

    Alexander Lossos, MD, alos@hadassah.org.il

    Alexander Lossos, MD

    Recruiting

  • Rabin Medical Center

    Petah Tikva, 49372

    Shlomit Yust-Katz, MD, shlomit2@clalit.org.il

    Shlomit Yust-Katz, MD

    Recruiting

  • Schneider Children's Medical Center of Israel

    Petah Tikvah, 4920235

    Helen Toledano, MD, Helent@clalit.org.il

    Helen Toledano, MD

    Recruiting

  • Sheba Medical Center

    Ramat Gan, Tel Aviv, 5262100

    Michal Yalon, MD, PhD, michal.yalon@sheba.health.gov.il

    Michal Yalon, MD, PhD

    Recruiting

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

    Deborah Blumenthal, MD, Dvorab@tlvmc.gov.il

    Deborah Blumenthal, MD

    Recruiting

Other trials in Israel

Italy7 sites, 6 recruiting

  • Ospedale Bellaria

    Bologna, Emilia-Romagna, 40139

    Enrico Franceschi, MD, e.franceschi@ausl.bo.it

    Enrico Franceschi, MD

    Recruiting

  • Ospedale San Raffaele S.r.l.

    Milan, Lombardy, 20132

    Gaetano Finocchiaro, MD, gaetano.finocchiaro@hsr.it

    Gaetano Finocchiaro, MD

    Recruiting

  • Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta

    Milan, Lombardy, 20133

    Paola Gaviani, MD, paola.gaviani@istituto-besta.it

    Paola Gaviani, MD

    Recruiting

  • Istituto Oncologico Veneto

    Padova, Veneto, 35128

    Giuseppe Lombardi, MD, PhD, giuseppe.lombardi@iov.veneto.it

    Giuseppe Lombardi, MD, PhD

    Recruiting

  • Istituto Nazionale Tumori Regina Elena

    Rome, Lazio, 00144

    Withdrawn

  • Istituto Clinico Humanitas

    Rozzano, Lombardy, 20089

    Matteo Simonelli, MD, matteo.simonelli@humanitas.it

    Matteo Simonelli, MD

    Recruiting

  • Azienda Ospedaliera Città della Salute e della Scienza di Torino

    Turin, Piedmont, 10126

    Alessia Pellerino, MD, alessia.pellerino@unito.it

    Alessia Pellerino, MD

    Recruiting

Other trials in Italy

Australia6 sites, 6 recruiting

  • Olivia Newton-John Cancer Research Institute (ONJCRI)

    Heidelberg, Victoria, 3084

    Lawrence Cher, lawrence.cher@austin.org.au

    Lawrence Cher

    Recruiting

  • Royal Brisbane and Women's Hospital

    Herston, Queensland

    Zarnie Lwin, MD, zarnie.lwin@health.qld.gov.au

    Zarnie Lwin, MD

    Recruiting

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

    Thomas Walwyn, thomas.walwyn@ths.tas.gov.au

    Thomas Walwyn

    Recruiting

  • Perth Children's Hospital

    Nedlands, Western Australia, 6009

    Santosh Valvi, Santosh.Valvi@health.wa.gov.au

    Santosh Valvi

    Recruiting

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

    David Ziegler, BS, MB, MD, d.ziegler@unsw.edu.au

    David Ziegler, BS, MB, MD

    Recruiting

  • Royal North Shore Hospital

    Sydney, New South Wales, 2065

    Helen Wheeler, MD, helen.wheeler@health.nsw.gov.au

    Helen Wheeler, MD

    Recruiting

Other trials in Australia

Japan6 sites, 6 recruiting

  • National Cancer Center Hospital

    Chūō, 104-0045

    Yoshitaka Narita, MD, yonarita@ncc.go.jp

    Yoshitaka Narita, MD

    Recruiting

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 812-8582

    Yuhki Koga, yuhkikoga@gmail.com

    Yuhki Koga

    Recruiting

  • Kyoto University Hospital

    Kyoto, 606-8507

    Yoshiki Arakawa, MD, yarakawa@kuhp.kyoto-u.ac.jp

    Yoshi Arakawa, MD

    Recruiting

  • Osaka City General Hospital

    Osaka, 534-0021

    Keiko Okada, keiko-okada@med.osakacity-hp.or.jp

    Keiko Okada

    Recruiting

  • Hokkaido University Hospital

    Sapporo, 060-8648

    Atsushi Manabe, atmanabe@med.hokudai.ac.jp

    Atsushi Manabe

    Recruiting

  • The University of Tokyo Hospital

    Tokyo

    Hirokazu Takami, MD, hirokazu.takami@gmail.com

    hirokazu Takami, MD

    Recruiting

Other trials in Japan

Denmark4 sites, 4 recruiting

  • Aalborg Universitetshospital

    Aalborg, North Denmark, 9000

    Charlotte Aaquist Haslund, MD, cah@rn.dk

    Charlotte Aaquist Haslund, MD

    Recruiting

  • Copenhagen University Hospital

    Copenhagen, Capital, 2100

    Søren Møller, MD, soeren.moeller.01@regionh.dk

    Søren Møller, MD

    Recruiting

  • F345 H.C. Andersen's Children's Hospital

    Odense, Region Syddanmark, 5000

    Michael Callesen, michael.callesen@rsyd.dk

    Michael Callesen

    Recruiting

  • Odense Universitetshospital

    Odense, Region Syddanmark, 5000

    Rikke Dahlrot, MD, rikke.dahlrot@rsyd.dk

    Rikke Dahlrot, MD

    Recruiting

Other trials in Denmark

Brazil3 sites, 3 recruiting

  • Hospital do GRAACC

    São Paulo, 04023-062

    Andrea Maria Cappellano, andreacappellano@graacc.org.br

    Andrea Maria Cappellano

    Recruiting

  • Hcor Research Institute

    São Paulo

    Gabriel Batistella, gbatistella@hcor.com.br

    Gabriel Batistella

    Recruiting

  • Instituto Do Cancer Do Estado De São Paulo

    São Paulo

    Olavo Feher, MD, olavo.feher071@hc.fm.usp.br

    Olavo Feher, MD

    Recruiting

Other trials in Brazil

Singapore3 sites, 3 recruiting

  • KK Women's and Children's Hospital

    Singapore, 229899

    Enrica Tan Ee Kar, MBBS, enrica.tan.e.k@singhealth.com.sg

    Enrica Tan Ee Kar, MBBS

    Recruiting

  • National Cancer Centre

    Singapore, 308433

    Chee Kian Tham, MD, tham.chee.kian@singhealth.com.sg

    Chee Kian Tham, MD

    Recruiting

  • National Neuroscience Institute

    Singapore, 308433

    Xuling Lin, MD, lin.xu.ling@singhealth.com.sg

    Xuling Lin, MD

    Recruiting

Other trials in Singapore

Austria2 sites, 2 recruiting

  • Medical University of Vienna - Adults

    Vienna, State of Vienna, 01090

    Anna Bergmeister-Berghoff, MD, anna.berghoff@meduniwien.ac.at

    Anna Bergmeister-Berghoff, MD

    Recruiting

  • Medical University of Vienna - Pediatrics

    Vienna, State of Vienna

    Johannes Gojo, johannes.gojo@meduniwien.ac.at

    Johannes Gojo

    Recruiting

Other trials in Austria

Netherlands2 sites, 2 recruiting

  • Erasmus MC

    Rotterdam, South Holland, 3015 GD

    Jacoline Bromberg, j.bromberg@erasmusmc.nl

    Jacoline Bromberg

    Recruiting

  • Universitair Medisch Centrum Utrecht Cancer Center

    Utrecht, 3584 CX

    Tom J Snijders, t.j.snijders@umcutrecht.nl

    Tom J Snijders

    Recruiting

Other trials in Netherlands

Switzerland2 sites, 2 recruiting

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, Canton of Vaud, 1011

    Andreas Hottinger, MD, PhD, andreas.hottinger@chuv.ch

    Andreas Hottinger, MD, PhD

    Recruiting

  • Universitätsspital Zürich

    Zurich, 8091

    Emilie Le Rhun, MD, PhD, emilie.lerhun@usz.ch

    Emilie Le Rhun, MD, PhD

    Recruiting

Other trials in Switzerland

Argentina1 site, 1 recruiting

  • FLENI Neurologia

    Buenos Aires, C1426ABP

    Agustin Maximo Cardoso, MD, agustin@cardoso.com.ar

    Agustin Maximo Cardoso, MD

    Recruiting

Other trials in Argentina

Hong Kong1 site, 1 recruiting

  • Queen Mary Hospital

    Hong Kong, 999077

    Aya El Helali, MD, ahelali@hku.hk

    Aya El Helali, MD

    Recruiting

Other trials in Hong Kong

About this study

Official title: 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.

Conditions
H3 K27M, Glioma
Being tested
Dordaviprone (ONC201), Dordaviprone (ONC201) + Placebo, Placebo
Keywords
H3 K27M, H3 K28M, H3 K27-altered, histone, H3F3A, HIST1H3B, HIST1H3C, H3.1, H3.3, DMG, thalamus, thalamic, midline
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dordaviprone (ONC201)Drug

    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.

  • Dordaviprone (ONC201) + PlaceboDrug

    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

  • PlaceboOther

    Participants will receive placebo (same number of capsules as the dordaviprone dose) on dosing days

Study groups in NCT05580562
Study groupRoleWhat they receive
Dordaviprone Twice Weekly GroupExperimentalNot described
Receives: Drug: Dordaviprone (ONC201)
Dordaviprone Once Weekly GroupExperimentalNot described
Receives: Drug: Dordaviprone (ONC201) + Placebo
Placebo GroupPlacebo comparatorNot described
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    Overall Survival is defined as the time from randomization to death due to any cause.

    Measured: From date of randomization until date of death from any cause, assessed up to approximately 44 months

Secondary outcomes (22)

  1. Progression Free Survival (PFS) using RANO 2.0 Criteria for All Participants

    PFS is defined as time from randomization to disease progression (PD) or death.

    Measured: From date of randomization until the date of first documented progression assessed up to approximately 44 months.

  2. PFS Using RANO 2.0 Criteria for Participants with Measurable Contrast-Enhancing Disease

    PFS is defined as time from randomization to disease progression (PD) or death.

    Measured: From date of randomization up to 44 months

  3. Incidence of adverse events

    Incidence of overall, treatment-related, Grade 3 or higher in severity, serious, fatal, those resulting in treatment discontinuation, and events of special interest

    Measured: From date of randomization up to 44 months

  4. Change from baseline in clinical laboratory parameters

    Percentage of participants with clinically significant laboratory results

    Measured: From date of randomization up to 44 months

  5. Distribution of Graded Clinical Laboratory Parameter

    Breakdown of how many participants fall into each severity grade. Grade 1 for mild up to Grade 4 for severe or life threatening.

    Measured: From date of randomization up to 44 months

  6. Corticosteroid response

    Corticosteroid response will be measured by a confirmed 50% decrease in use of dexamethasone or equivalent

    Measured: From date of randomization up to 44 months

  7. Time to First Corticosteroid Response

    Time from the first dose to the nominal analysis timepoint when the response criteria are first met.

    Measured: From date of randomization up to 44 months

  8. Duration of First Corticosteroid Response

    Time from first response to end of first response.

    Measured: From date of randomization up to 44 months

  9. Cumulative Duration of Corticosteroid Responses

    Total durations of response, irrespective of censoring, to account for participants with multiple responses during the study.

    Measured: From date of randomization up to 44 months

  10. Corticosteroid Dose and Change from Baseline Over Time

    Measured: From date of randomization up to 44 months

  11. Time to Corticosteroid Use Deterioration

    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.

    Measured: From date of randomization up to 44 months

  12. Performance status response

    Performance status response will be measured by confirmed increase in Karnofsky Performance Status (KPS) or Lansky Performance Status (LPS).

    Measured: From date of randomization up to 44 months

  13. Time to first performance status response

    time from the first dose of study intervention to the nominal analysis timepoint when the response criteria are first met.

    Measured: From date of randomization up to 44 months

  14. Duration of first performance status response

    Time from response to end of response.

    Measured: From date of randomization up to 44 months

  15. Cumulative duration of performance status responses

    Total durations of response, irrespective of censoring, to account for patients with multiple responses during the study

    Measured: From date of randomization up to 44 months

  16. Performance status and change from baseline over time

    Measured: From date of randomization up to 44 months

  17. Time to performance status deterioration

    As time from the first dose of study intervention to time when KPS/LPS score < baseline or death.

    Measured: From date of randomization up to 44 months

  18. Change from Baseline in European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30)

    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.

    Measured: Day 1 (pre-dose), up to 44 months

  19. Change from Baseline in Quality of Life-Core Questionnaire Brain Module (QLQ-BN20)

    The QLQ-bN20 will be administered to participants ≥ 18 years of age and will measure health related quality of life.

    Measured: Day 1 (pre-dose), up to 44 months

  20. Change from Baseline in MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT)

    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.

    Measured: Day 1 (pre-dose), up to 44 months

  21. Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module

    The PedsQL will be administered to participants 2 to < 18 years of age. It measures 4 scales: physical, emotional, social, and school functioning.

    Measured: Day 1 (pre-dose), up to 44 months

  22. Change from Baseline in Neurologic Assessment in Neuro-Oncology (NANO) Score

    The NANO score evaluates gait, strength, ataxia in the upper extremity, sensation, visual field, facial strength, language, level of consciousness, and behavior.

    Measured: Day 1 (pre-dose), up to 44 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2022
  2. Study start23 Jan 2023
  3. Primary completionJun 2028 (estimated)
  4. Study completionJun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
510 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05580562
Sponsor's protocol ID
ONC201-108
Acronym
ACTION
Status last verified
Apr 2026
First submitted
27 Sep 2022
Last updated
16 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dordaviprone (ONC201) in people with H3 K27M and Glioma, run by Jazz Pharmaceuticals at 162 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 162 sites in United States, United Kingdom, Germany, South Korea, Spain and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trial Disclosure & Transparency (215-832-3750, ClinicalTrialDisclosure@jazzpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: From date of randomization until date of death from any cause, assessed up to approximately 44 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05580562.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in