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The ACTION Study: ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy
EU CTIS ID: 2022-502051-56-00
What this study is testing
To evaluate the efficacy of dordaviprone administered following radiotherapy in participants with H3 K27Mmutant diffuse glioma
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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 ≥ 11 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 (IHC or NGS in a CLIA-certified or equivalent laboratory). [Site to provide (as available): ≥ 11 unstained 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. [Site to also provide all available MRIs completed prior to initiating treatment with study intervention.]
- Received standard frontline radiotherapy within 2 to 6 weeks prior to randomization. Standard frontline radiotherapy is defined as a dose of 54 to 60 Gy at 1.8 to 2.2 Gy/fraction. Radiotherapy must be initiated within 12 weeks from initial diagnosis of H3 K27M-mutant diffuse glioma and within 8 weeks of most recent surgical resection/biopsy.
You likely can't join if
- 1. Primary spinal tumor
- 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.
See the full eligibility criteria
Who can 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 ≥ 11 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 (IHC or NGS in a CLIA-certified or equivalent laboratory). [Site to provide (as available): ≥ 11 unstained 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. [Site to also provide all available MRIs completed prior to initiating treatment with study intervention.]
- Received standard frontline radiotherapy within 2 to 6 weeks prior to randomization. Standard frontline radiotherapy is defined as a dose of 54 to 60 Gy at 1.8 to 2.2 Gy/fraction. Radiotherapy must be initiated within 12 weeks from initial diagnosis of H3 K27M-mutant diffuse glioma and within 8 weeks of most recent surgical resection/biopsy.
- 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).
What rules you out
- 1. Primary spinal tumor
- 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.
- 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: a. Dordaviprone (ONC201) or ONC206 at any time; b. bevacizumab (includes biosimilars) at any time; c. Temozolomide within past 3 weeks; d. Tumor treating fields at any time; e. DRD2 antagonist within past 2 weeks; f. Any investigational therapy within past 4 weeks; g. Strong CYP3A4/5 inhibitors within 3 days; h. Strong CYP3A4/5 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: a. Absolute neutrophil count <1.0 × 10^9/L or platelets <75 × 10^9/L; b. 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); c. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × ULN; d. Creatinine clearance ≤60 mL/min as calculated by the Cockcroft Gault equation (or estimated glomerular filtration rate <60 mL/min/1.73 m2).
The study team makes the final eligibility decision.
Where it's taking place
- Brazil
- Korea, Republic of
- Canada
- Australia
- Argentina
- Hong Kong
- Switzerland
- Israel
- United Kingdom
- United States
- Japan
- Singapore
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years, 0-17 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Brazil; Korea, Republic of; Canada; Australia; Argentina; Hong Kong and 6 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.