BridgeMD
New treatment option for H3 K27M
Official title ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)
ClinicalTrials.gov ID: NCT05580562
What this study is testing
What is Dordaviprone (ONC201)?
Dordaviprone (ONC201) is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for h3 k27m.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 3: a large, late-stage study
- You might receive a placebo (an inactive treatment) instead of the study drug, decided by chance. You may not know which one you got.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Adults
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...
- 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...
- At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to starting radiotherapy for submission to sponsor's imaging vendor for...
- 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...
You likely can't join if
- 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.
See the full eligibility criteria
- 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...
- 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...
- 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...
- Received frontline radiotherapy
- 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...
- 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.
- 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...
- 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.
The study team makes the final eligibility decision.
Where it's taking place
- Phoenix, Arizona, United States
- La Jolla, California, United States
- Los Angeles, California, United States
- Orange, California, United States
- San Francisco, California, United States
- Santa Monica, California, United States
- Stanford, California, United States
- New Haven, Connecticut, United States
- Washington D.C., District of Columbia, United States
- Jacksonville, Florida, United States
- Miami, Florida, United States
- Tampa, Florida, United States
- Weston, Florida, United States
- Atlanta, Georgia, United States
- Honolulu, Hawaii, United States
- Chicago, Illinois, United States
- Indianapolis, Indiana, United States
- Iowa City, Iowa, United States
- Louisville, Kentucky, United States
- New Orleans, Louisiana, United States
+ 107 more site(s).
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, not specified. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Phoenix, Arizona, United States; La Jolla, California, United States; Los Angeles, California, United States; Orange, California, United States; San Francisco, California, United States; Santa Monica, California, United States and 121 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 ClinicalTrials.gov; the study team decides eligibility.