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

M
Michael Ferguson, MD

Primary Investigator

Enrolling By Invitation
All
Phase 3
450 participants needed
2 Locations

Overview

What is the purpose of this 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 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.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Description

What will happen during the study?
Experimental: ONC201 Twice Weekly Group    Drug: ONC201
Participants ≥ 52.5 kg will receive 625 mg of ONC201 (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: ONC201 Once Weekly Group    Drug: ONC201 + Placebo
Participants ≥ 52.5 kg will receive 625 mg of ONC201 (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

Placebo Comparator: Placebo Group    Other: Placebo
Participants will receive placebo (same number of capsules as the ONC201 dose) on dosing days

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    H3 K27M, Glioma
  • Gender: All

Inclusion Criteria:
  1. Able to understand the study procedures and agree to participate in the study byviding written informed consent (by participant or legally authorizedve), 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 aK27M mutation in any histone H3-encoding gene detected by testing of tumorue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a ClinicalLaboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site tovide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slidesumor tissue.]
  4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior tog radiotherapy for submission to sponsor's imaging vendor for central read. Forwho had a surgical resection, this scan must be post-resection; forwho 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 weeksdiotherapy. [Site to also provide all available MRIsd prior to initiating treatment with study intervention.]
  6. Completed standard frontline radiotherapy within 2 to 6 weeks prior to randomization.dard frontline radiotherapy is defined as a dose of 54 to 60 Gy at 1.8 to 2.2Gy/fraction. Radiotherapy must be initiated within 12 weeks from initial diagnosis ofH3 K27M-mutant diffuse glioma and within 8 weeks of most recent surgical/biopsy.
  7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time ofdomization.
  8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 daysdomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day(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 epicenterd 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 todomization
    1. ONC201 or ONC206 at any time.
    2. Bevacizumab (includes biosimilars) at any time.
    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 CYP3A4/5 inhibitors within 3 days.
    8. Strong CYP3A4/5 inducers (includes enzyme-inducing antiepileptic drugs) within 2weeks.
  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'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 studyvention or within 3 months after the last dose. Participants of childbearingust have a negative serum pregnancy test within 72 hours prior to receivinghe first dose of study intervention.
  13. Uncontrolled intercurrent illness including, but not limited to, ongoing or activequiring systemic therapy or psychiatric illness/social situations thatwould limit compliance with study requirements.
  14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of thevestigator, may interfere with participant safety or the ability to complete theudy according to the protocol.

Updated on 01 Aug 2024. Study ID: ONC201-108, PHO-CHIMERIX-ONC201, 18491
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