Actively Recruiting

Phase 3
All Genders
NCT05580562

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

Led by Jazz Pharmaceuticals · Updated on 2026-04-16

510

Participants Needed

162

Research Sites

279 weeks

Total Duration

On this page

Sponsors

J

Jazz Pharmaceuticals

Lead Sponsor

C

Chimerix, Inc.

Collaborating Sponsor

AI-Summary

What this Trial Is About

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

Official Title

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

Who Can Participate

All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Able to understand study procedures and provide written informed consent or assent when applicable
  • Body weight of at least 10 kg at randomization
  • Histologically confirmed diagnosis of newly diagnosed H3 K27M-mutant diffuse glioma by tumor tissue testing
  • At least one high-quality, contrast-enhanced brain MRI obtained before starting radiotherapy
  • At least one high-quality, contrast-enhanced brain MRI obtained 2 to 6 weeks after completing frontline radiotherapy (non-enhanced MRI allowed if venous access is not possible)
  • Receipt of standard frontline radiotherapy initiated within 12 weeks of diagnosis and completed 2 to 6 weeks before randomization
  • Karnofsky or Lansky Performance Status score of 70 or higher at randomization
  • Stable or decreasing corticosteroid and anti-seizure medication doses for 7 days before randomization, if applicable
Not Eligible

You will not qualify if you...

  • Primary spinal tumor
  • Diffuse intrinsic pontine glioma (DIPG) with pontine epicenter and diffuse pons involvement
  • Evidence of leptomeningeal spread or cerebrospinal fluid dissemination of disease
  • Any known concurrent malignancy
  • New tumor lesions outside the radiation field
  • Prior whole-brain radiotherapy
  • Prior proton therapy for glioma
  • Prior use of dordaviprone (ONC201), ONC206, systemic bevacizumab since diagnosis, temozolomide within 3 weeks, tumor treating fields, DRD2 antagonists within 2 weeks, investigational therapies within 4 weeks, strong CYP3A4 inhibitors within 3 days, or strong CYP3A4 inducers within 2 weeks
  • Laboratory abnormalities within 2 weeks before randomization: absolute neutrophil count below 1.0 x 10^9/L, platelets below 75 x 10^9/L, total bilirubin above 1.5 times upper limit of normal (ULN) except Gilbert's syndrome with normal direct bilirubin, AST or ALT above 2.5 times ULN, creatinine clearance 60 mL/min or less
  • QTc interval greater than 480 msec during screening
  • Known allergy to any ingredients in the study treatment
  • Pregnant, breastfeeding, or planning pregnancy during treatment or within 3 months after last dose; must have negative pregnancy test if of childbearing potential
  • Uncontrolled illness or infection requiring systemic therapy or psychiatric/social conditions limiting compliance
  • Any other condition that may interfere with safety or study completion as judged by the investigator

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 162 locations

1

Banner MD Anderson Cancer Center

Phoenix, Arizona, United States, 85006

Completed

2

Barrow Neurological Institute

Phoenix, Arizona, United States, 85013

Active, Not Recruiting

3

Phoenix Childrens Hospital

Phoenix, Arizona, United States, 85016

Completed

4

Mayo Clinic Arizona

Phoenix, Arizona, United States, 85054

Completed

5

UC San Diego Moores Cancer Center

La Jolla, California, United States, 92093

Active, Not Recruiting

6

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States, 90027

Completed

7

UCLA University of California Los Angeles

Los Angeles, California, United States, 90095

Completed

8

Children's Hospital of Orange County

Orange, California, United States, 92868

Completed

9

University of California Irvine

Orange, California, United States, 92868

Active, Not Recruiting

10

UCSF Benioff Children's Hospital

San Francisco, California, United States, 94143

Active, Not Recruiting

11

University of California San Francisco

San Francisco, California, United States, 94143

Active, Not Recruiting

12

Providence Saint John's Cancer Institute

Santa Monica, California, United States, 90404

Active, Not Recruiting

13

Stanford Cancer Center

Stanford, California, United States, 94350

Completed

14

Yale University

New Haven, Connecticut, United States, 06511

Active, Not Recruiting

15

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States, 20007

Completed

16

Mayo Clinic Jacksonville

Jacksonville, Florida, United States, 32224

Active, Not Recruiting

17

Miami Cancer Institute

Miami, Florida, United States, 33176

Active, Not Recruiting

18

St Joseph's Children's Hospital of Tampa

Tampa, Florida, United States, 33607

Completed

19

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Active, Not Recruiting

20

Cleveland Clinic Florida

Weston, Florida, United States, 33331

Completed

21

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30342

Completed

22

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, United States, 96826

Completed

23

Feinberg School of Medicine Northwestern University

Chicago, Illinois, United States, 60611

Active, Not Recruiting

24

Indiana University School of Medicine - Indianapolis

Indianapolis, Indiana, United States, 46202

Active, Not Recruiting

25

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States, 52242

Active, Not Recruiting

26

Norton Healthcare

Louisville, Kentucky, United States, 40241

Active, Not Recruiting

27

Ochsner Medical Center - New Orleans

New Orleans, Louisiana, United States, 70121

Completed

28

University of Maryland School of Medicine

Baltimore, Maryland, United States, 21201

Completed

29

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States, 02114

Active, Not Recruiting

30

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Active, Not Recruiting

31

University of Michigan Hospital

Ann Arbor, Michigan, United States, 48109

Active, Not Recruiting

32

University of Minnesota

Minneapolis, Minnesota, United States, 55455

Active, Not Recruiting

33

Mayo Clinic - Cancer Center - Rochester

Rochester, Minnesota, United States, 55905

Active, Not Recruiting

34

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

St Louis, Missouri, United States, 63110

Active, Not Recruiting

35

Benefis Hospital Sletten Cancer Institute

Great Falls, Montana, United States, 59405

Withdrawn

36

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68114

Completed

37

Jersey Shore University Medical Center

Neptune City, New Jersey, United States, 07753

Active, Not Recruiting

38

Overlook Medical Center

Summit, New Jersey, United States, 07901

Active, Not Recruiting

39

Albany Medical Center

Albany, New York, United States, 12208

Completed

40

Children's Hospital at Montefiore Medical Center

New York, New York, United States, 10029

Completed

41

Montefiore Medical Park

New York, New York, United States, 10029

Active, Not Recruiting

42

Laura & Isaac Perlmutter Cancer Center - NYU ACC

New York, New York, United States, 10032-3726

Active, Not Recruiting

43

Columbia University Medical Center

New York, New York, United States, 10032

Active, Not Recruiting

44

Lenox Hill Hospital

New York, New York, United States, 10075

Completed

45

University of Rochester Medical Center

Rochester, New York, United States, 14642

Completed

46

Levine Cancer Institute/ Atrium Health

Charlotte, North Carolina, United States, 28204

Active, Not Recruiting

47

Duke Cancer Institute

Durham, North Carolina, United States, 27710

Active, Not Recruiting

48

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Active, Not Recruiting

49

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Active, Not Recruiting

50

Ohio State University

Columbus, Ohio, United States, 43210

Active, Not Recruiting

51

University of Oklahoma Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

Active, Not Recruiting

52

Providence Health and Services St. Vincent Medical Center

Portland, Oregon, United States, 97239

Active, Not Recruiting

53

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Active, Not Recruiting

54

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Active, Not Recruiting

55

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15232

Completed

56

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

Completed

57

Dell Children's Medical Center of Central Texas

Austin, Texas, United States, 78723

Completed

58

Neuro-Oncology Associates

Dallas, Texas, United States, 75246

Active, Not Recruiting

59

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Active, Not Recruiting

60

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Active, Not Recruiting

61

UT Health Houston Neurosciences - Texas Medical Center

Houston, Texas, United States, 77030

Completed

62

University of Texas - San Antonio - Health Science Center

San Antonio, Texas, United States, 78229

Active, Not Recruiting

63

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

Active, Not Recruiting

64

Inova Schar Cancer Institute

Fairfax, Virginia, United States, 22031

Active, Not Recruiting

65

Children's Hospital of The King's Daughter

Norfolk, Virginia, United States, 23507

Completed

66

University of Washington

Seattle, Washington, United States, 98195

Active, Not Recruiting

67

University Of Wisconsin - Madison

Madison, Wisconsin, United States, 53792

Active, Not Recruiting

68

FLENI Neurologia

Buenos Aires, Argentina, C1426ABP

Actively Recruiting

69

Sydney Children's Hospital

Randwick, New South Wales, Australia, 2031

Actively Recruiting

70

Royal North Shore Hospital

Sydney, New South Wales, Australia, 2065

Actively Recruiting

71

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Actively Recruiting

72

Royal Hobart Hospital

Hobart, Tasmania, Australia, 7000

Actively Recruiting

73

Olivia Newton-John Cancer Research Institute (ONJCRI)

Heidelberg, Victoria, Australia, 3084

Actively Recruiting

74

Perth Children's Hospital

Nedlands, Western Australia, Australia, 6009

Actively Recruiting

75

Medical University of Vienna - Adults

Vienna, State of Vienna, Austria, 01090

Actively Recruiting

76

Medical University of Vienna - Pediatrics

Vienna, State of Vienna, Austria

Actively Recruiting

77

Hospital do GRAACC

São Paulo, Brazil, 04023-062

Actively Recruiting

78

Hcor Research Institute

São Paulo, Brazil

Actively Recruiting

79

Instituto Do Cancer Do Estado De São Paulo

São Paulo, Brazil

Actively Recruiting

80

Tom Baker Cancer Cetre

Calgary, Alberta, Canada, T2N 2T9

Actively Recruiting

81

BC Cancer - The Vancouver Center

Vancouver, British Columbia, Canada, V5Z 4E6

Actively Recruiting

82

Children's & Women's Health Care of BC

Vancouver, British Columbia, Canada, V6H 0B3

Actively Recruiting

83

London Health Sciences Centre

London, Ontario, Canada, N6A 5W9

Actively Recruiting

84

Childrens Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

Actively Recruiting

85

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

Actively Recruiting

86

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 1X8

Actively Recruiting

87

Hopital Notre Dame, Lachapelle

Montreal, Quebec, Canada, H2X 3E4

Actively Recruiting

88

Copenhagen University Hospital

Copenhagen, Capital, Denmark, 2100

Actively Recruiting

89

Aalborg Universitetshospital

Aalborg, North Denmark, Denmark, 9000

Actively Recruiting

90

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

Odense, Region Syddanmark, Denmark, 5000

Actively Recruiting

91

Odense Universitetshospital

Odense, Region Syddanmark, Denmark, 5000

Actively Recruiting

92

University Clinic Heidelberg

Heidelberg, Baden-Wurttemberg, Germany, 69120

Actively Recruiting

93

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany, 69120

Actively Recruiting

94

Universitätsklinikum Augsburg

Augsburg, Bavaria, Germany, 86156

Actively Recruiting

95

University Clinic Regensburg

Regensburg, Bavaria, Germany, 93053

Actively Recruiting

96

Klinikum der Johann-Wolfgang Goethe-Universitat

Frankfurt am Main, Hesse, Germany, 60528

Actively Recruiting

97

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, Germany, 53127

Actively Recruiting

98

Uniklinik Köln

Cologne, North Rhine-Westphalia, Germany, 50937

Actively Recruiting

99

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany, 45147

Actively Recruiting

100

Vivantes Klinikum Neukölln

Berlin, Germany, 12351

Actively Recruiting

101

Klinikum Mannheim Universitätsklinikum gGmbH

Manheim, Germany, 68167

Actively Recruiting

102

Universitätsklinikum Tübingen

Tübingen, Germany, 72076

Actively Recruiting

103

Queen Mary Hospital

Hong Kong, Hong Kong, 999077

Actively Recruiting

104

Sheba Medical Center

Ramat Gan, Tel Aviv, Israel, 5262100

Actively Recruiting

105

Soroka University Medical Centre

Beersheba, Israel, 50937

Actively Recruiting

106

Rambam Medical Center

Haifa, Israel, 31096

Actively Recruiting

107

Hadassah Ein Kerem Medical Center

Jerusalem, Israel, 91120

Actively Recruiting

108

Rabin Medical Center

Petah Tikva, Israel, 49372

Actively Recruiting

109

Schneider Children's Medical Center of Israel

Petah Tikvah, Israel, 4920235

Actively Recruiting

110

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 64239

Actively Recruiting

111

Ospedale Bellaria

Bologna, Emilia-Romagna, Italy, 40139

Actively Recruiting

112

Istituto Nazionale Tumori Regina Elena

Rome, Lazio, Italy, 00144

Withdrawn

113

Ospedale San Raffaele S.r.l.

Milan, Lombardy, Italy, 20132

Actively Recruiting

114

Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta

Milan, Lombardy, Italy, 20133

Actively Recruiting

115

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy, 20089

Actively Recruiting

116

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy, 10126

Actively Recruiting

117

Istituto Oncologico Veneto

Padova, Veneto, Italy, 35128

Actively Recruiting

118

National Cancer Center Hospital

Chūō, Japan, 104-0045

Actively Recruiting

119

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan, 812-8582

Actively Recruiting

120

Kyoto University Hospital

Kyoto, Japan, 606-8507

Actively Recruiting

121

Osaka City General Hospital

Osaka, Japan, 534-0021

Actively Recruiting

122

Hokkaido University Hospital

Sapporo, Japan, 060-8648

Actively Recruiting

123

The University of Tokyo Hospital

Tokyo, Japan

Actively Recruiting

124

Erasmus MC

Rotterdam, South Holland, Netherlands, 3015 GD

Actively Recruiting

125

Universitair Medisch Centrum Utrecht Cancer Center

Utrecht, Netherlands, 3584 CX

Actively Recruiting

126

KK Women's and Children's Hospital

Singapore, Singapore, 229899

Actively Recruiting

127

National Cancer Centre

Singapore, Singapore, 308433

Actively Recruiting

128

National Neuroscience Institute

Singapore, Singapore, 308433

Actively Recruiting

129

CHA Bundang Medical Center

Bundang-Gu, Seongnam-Si, Gyeonggido, South Korea, 13496

Actively Recruiting

130

Seoul National University Bundang Hospital

Bundang-gu, Seongnam-si, Gyeonggido, South Korea, 13620

Actively Recruiting

131

Seoul National University Hospital

Bundang-gu, Seongnam-si, Gyeonggido, South Korea, 13620

Actively Recruiting

132

National Cancer Center

Ilsandong-Gu, Goyang-Si, Gyeonggido, South Korea, 10408

Actively Recruiting

133

Gangnam Severance Hospital, Yonsei University Health System

Gangnam, Seoul Teugbyeolsi, South Korea, 06273

Actively Recruiting

134

Samsung Medical Center

Gangnam-Gu, Seoul Teugbyeolsi, South Korea, 06351

Actively Recruiting

135

Seoul National University Hospital

Jongno-Gu, Seoul Teugbyeolsi, South Korea, 03080

Actively Recruiting

136

Asan Medical Center

Seoul, Seoul Teugbyeolsi, South Korea, 5505

Actively Recruiting

137

Severance Hospital Yonsei University Health System

Seoul, South Korea, 03722

Actively Recruiting

138

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

Seoul, South Korea, 6591

Actively Recruiting

139

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, Spain, 8950

Actively Recruiting

140

Clinica Universidad Navarra

Pamplona, Navarre, Spain, 31008

Actively Recruiting

141

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Actively Recruiting

142

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 8035

Actively Recruiting

143

Hospital Infantil Universitario Niño Jesus

Madrid, Spain, 28009

Actively Recruiting

144

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Actively Recruiting

145

Hospital Universitario HM Sanchinarro

Madrid, Spain, 28050

Actively Recruiting

146

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, Spain, 37007

Actively Recruiting

147

Hospital Universitari i Politecnic La Fe de Valencia - Adults

Valencia, Spain, 46026

Actively Recruiting

148

Hospital Universitari i Politecnic La Fe de Valencia - Pediatrics

Valencia, Spain, 46026

Actively Recruiting

149

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, Switzerland, 1011

Actively Recruiting

150

Universitätsspital Zürich

Zurich, Switzerland, 8091

Actively Recruiting

151

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Actively Recruiting

152

Beatson West of Scotland Cancer Centre

Glasgow, Lanarkshire, United Kingdom, G12 0YN

Actively Recruiting

153

Royal Hospital for Children (Glasgow)

Glasgow, Lanarkshire, United Kingdom, G51 4TF

Actively Recruiting

154

Clatterbridge Cancer Centre - Liverpool

Liverpool, Lancashire, United Kingdom, L7 8YA

Actively Recruiting

155

The Christie NHS Foundation Trust

Manchester, Lancashire, United Kingdom, M20 4BX

Actively Recruiting

156

The Royal Marsden in Sutton, Surrey

Sutton, Surrey, United Kingdom, SM2 5PT

Actively Recruiting

157

Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE1 4LP

Actively Recruiting

158

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN

Actively Recruiting

159

St James University Hospital

Leeds, West Yorkshire, United Kingdom, LS9 7TF

Actively Recruiting

160

The Leeds Teaching Hospitals NHS Trust, Leeds General Infimary

Leeds, United Kingdom, LS1 3EX

Actively Recruiting

161

Guy's Hospital

London, United Kingdom, SE19RT

Actively Recruiting

162

Churchill Hospital

Oxford, United Kingdom, Ox3 7LE

Actively Recruiting

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Research Team

C

Clinical Trial Disclosure & Transparency

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

TRIPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

3

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