Stopped: The Sponsor terminated the study to prioritize enrollment in a randomized Phase 3 trial of ONC201 in an earlier setting. This decision was unrelated to any safety concerns with dordaviprone (ONC201).
United States134 participantsStarted 2018-01-25
Plain-language summary
This was a Phase 1, open label, multicenter, 8-arm, dose escalation study of dordaviprone (ONC201) in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) and recurrent/refractory H3 K27M-mutant gliomas.
The primary endpoint of this study was to determine the recommended Phase 2 dose (RP2D) of dordaviprone (ONC201) in pediatric glioma patients as a single agent in combination with radiation.
Who can participate
Age range2 Years – 18 Years
SexALL
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Inclusion criteria
✓. 2 to less than 19 years of age.
✓. Patient body weight must be above the minimum necessary for the patient to receive the ONC201 dose indicated for the currently enrolling dose level. The minimum body weight ranges from 10-27.5kg depending on the dose level.
✓. Arm A and G: Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. No more than two episodes of recurrence from radiotherapy and/or chemotherapy are allowed. Use of bevacizumab solely for treatment of radiation necrosis, pseudoprogression, or treatment effect will not be considered a recurrence. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available.
✓. Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients \< 16 years of age. For Arm F, Karnofsky ≥ 60 for patients ≥ 16 years of age, and Lansky ≥ 60 for patients \< 16 years of age
✓. From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies. For patients who have received radiotherapy, patients in any arm must be at least 2 weeks from the completion of local palliative radiotherapy (re-irradiation for progressive disease or upfront radiation at initial diagnosis). For Arm F, patients must be at least 90 days from prior radiation to the first dose of ONC201unless the progressive lesion is outside of the high-dose radiation target volume or there is unequivocal evidence of progressive tumor on a biopsy specimen.
✓. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the subjects age.
✓. All adverse events Grade \> 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to grade 1 or baseline, except for alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment, are acceptable.
Exclusion criteria
✕. For Arms A, B, D, E, F and G: Evidence of diffuse leptomeningeal disease or evidence of CSF dissemination.
✕. Current or planned participation in a study of another investigational agent or using an investigational device.
✕. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients.
✕. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
✕. Any known clinically significant active infection including bacterial, fungal or viral including hepatitis B (HBV), hepatitis C (HCV) or any underlying disease or in the recent past which could compromise enrollment and safety of the patient
✕. Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC201. Receiving therapeutic agents known to prolong QT interval will be excluded, however the use of Zofran is permitted. History of CHF, or MI or stroke in the last 3 months will be excluded.
✕. Active illicit drug use or diagnosis of alcoholism.
✕. Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.