RECRUITING

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

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Conditions

H3 K27MGliomaH3 K28MH3 K27-alteredhistoneH3F3AHIST1H3BHIST1H3CH3.1H3.3DMGthalamusthalamicmidline

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 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.

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

Quick Facts

Study Start:2023-01-23
Study Completion:2026-08
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05580562

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.

Ages Eligible for Study:Not specified
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 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. 2. Body weight ≥ 10 kg at time of randomization.
  3. 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). \[Site to provide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slides from tumor tissue.\]
  4. 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. 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. 6. Received frontline radiotherapy
  7. 1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3 K27M-mutant diffuse glioma.
  8. 2. Completed radiotherapy within 2 to 6 weeks prior to randomization
  9. 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).
  10. 7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of randomization.
  11. 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).
  1. 1. Primary spinal tumor.
  2. 2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons.
  3. 3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
  4. 4. Any known concurrent malignancy.
  5. 5. New lesion(s) outside of the radiation field.
  6. 6. Received whole-brain radiotherapy.
  7. 7. Received proton therapy for glioma.
  8. 8. Use of any of the following treatments within the specified time periods prior to randomization:
  9. 1. ONC201 or ONC206 at any time.
  10. 2. Systemic bevacizumab (includes biosimilars) at any time since the initial diagnosis of H3 K27M-mutant diffuse glioma.
  11. 3. Temozolomide within past 3 weeks.
  12. 4. Tumor treating fields at any time.
  13. 5. DRD2 antagonist within past 2 weeks.
  14. 6. Any investigational therapy within past 4 weeks.
  15. 7. Strong CYP3A4 inhibitors within 3 days.
  16. 8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2 weeks.
  17. 9. Laboratory test results meeting any of the following parameters within 2 weeks prior to randomization:
  18. 1. Absolute neutrophil count \< 1.0 × 109/L or platelets \< 75 × 109/L.
  19. 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).
  20. 3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × ULN.
  21. 4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate \< 60 mL/min/1.73 m2).
  22. 10. QTc \> 480 msec (based on mean from triplicate electrocardiograms) during screening.
  23. 11. Known hypersensitivity to any excipients used in the study intervention formulation.
  24. 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.
  25. 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.
  26. 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.

Contacts and Locations

Study Contact

Tarapore, PhD
CONTACT
1-919-806-1074
clinicaltrials@chimerix.com

Study Locations (Sites)

Barrow Neurological Institute
Phoenix, Arizona, 085013
United States
Banner MD Anderson Cancer Center
Phoenix, Arizona, 85006
United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
United States
Mayo Clinic Arizona
Phoenix, Arizona, 85054
United States
University of California Irvine
Costa Mesa, California, 92628
United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093
United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
United States
UCLA University of California Los Angeles
Los Angeles, California, 90095
United States
Children's Hospital of Orange County
Orange, California, 92868
United States
UCSF Benioff Children's Hospital
San Francisco, California, 94143
United States
University of California San Francisco
San Francisco, California, 94143
United States
Providence Saint John's Cancer Institute
Santa Monica, California, 90404
United States
Stanford Cancer Center
Stanford, California, 94350
United States
Yale University
Fairfield, Connecticut, 06824
United States
MedStar Georgetown University Hospital
Washington, District of Columbia, 20007
United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
United States
Miami Cancer Institute
Miami, Florida, 33176
United States
St Joseph's Children's Hospital of Tampa
Tampa, Florida, 33607
United States
Moffitt Cancer Center
Tampa, Florida, 33612
United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342
United States
Kapi'olani Medical Center for Women and Children
Honolulu, Hawaii, 96826
United States
Feinberg School of Medicine Northwestern University
Chicago, Illinois, 60611
United States
Indiana University School of Medicine - Indianapolis
Indianapolis, Indiana, 46202
United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
United States
Norton Healthcare
Louisville, Kentucky, 40241
United States
Ochsner Medical Center - New Orleans
New Orleans, Louisiana, 70121
United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201
United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109
United States
University of Minnesota
Minneapolis, Minnesota, 55455
United States
Mayo Clinic - Cancer Center - Rochester
Rochester, Minnesota, 55905
United States
Washington University School of Medicine
Saint Louis, Missouri, 63110
United States
Benefis Hospital Sletten Cancer Institute
Great Falls, Montana, 59405
United States
University of Nebraska Medical Center
Omaha, Nebraska, 68114
United States
Jersey Shore University Medical Center
Neptune, New Jersey, 07753
United States
Overlook Medical Center
Summit, New Jersey, 07901
United States
Albany Medical Center
Albany, New York, 12208
United States
Children's Hospital at Montefiore Medical Center
New York, New York, 10029
United States
Montefiore Medical Park
New York, New York, 10029
United States
Laura & Isaac Perlmutter Cancer Center - NYU ACC
New York, New York, 10032-3726
United States
Columbia University Medical Center
New York, New York, 10032
United States
Columbia University Medical Center
New York, New York, 10032
United States
Lenox Hill Hospital
New York, New York, 10075
United States
University of Rochester Medical Center
Rochester, New York, 14642
United States
Levine Cancer Institute/ Atrium Health
Charlotte, North Carolina, 28204
United States
Duke Cancer Institute
Durham, North Carolina, 27710
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
United States
Cleveland Clinic
Cleveland, Ohio, 44195
United States
Ohio Statue University
Columbus, Ohio, 43210
United States
University of Oklahoma Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
United States
Providence Health and Services St. Vincent Medical Center
Portland, Oregon, 97239
United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
United States
Neuro-Oncology Associates
Dallas, Texas, 75246
United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
United States
UT Health Science Center Houston Department of Neurosurgery
Houston, Texas, 77030
United States
University of Texas - San Antonio - Health Science Center
San Antonio, Texas, 78229
United States
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112
United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
United States
Children's Hospital of The King's Daughter
Norfolk, Virginia, 23507
United States
University of Washington
Seattle, Washington, 98195
United States
University Of Wisconsin - Madison
Madison, Wisconsin, 53792
United States

Collaborators and Investigators

Sponsor: Chimerix

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 Registration Dates

Study Start Date2023-01-23
Study Completion Date2026-08

Study Record Updates

Study Start Date2023-01-23
Study Completion Date2026-08

Terms related to this study

Keywords Provided by Researchers

  • H3 K27M
  • H3 K28M
  • H3 K27-altered
  • histone
  • H3F3A
  • HIST1H3B
  • HIST1H3C
  • H3.1
  • H3.3
  • DMG
  • thalamus
  • thalamic
  • midline

Additional Relevant MeSH Terms

  • H3 K27M
  • Glioma