The objective of this expanded access program is to provide ONC201 to eligible patients with previously-treated glioma that exhibits the H3 K27M mutation and/or that is located in the midline region of the brain.
ONC201 is an oral, small molecule selective antagonist of DRD2 that induces tumor cell death.
1. Patient must have one type of diagnosis below: 1. A glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA certification); 2. A grade III or IV glioma involving the thalamus, hypothalamus, brainstem, cerebellum, midbrain, or spinal cord; 3. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. These patients are eligible with or without a tissue biopsy.
2. Unequivocal evidence of progressive disease on as defined by RANO criteria or have documented recurrent glioma on diagnostic biopsy.
3. Patient must have had previous therapy that includes radiotherapy.
4. Interval of at least 90 days from the completion of radiotherapy to the first dose of ONC201. If patients are within 90 days of radiotherapy, they may still be eligible if they meet one or more of the following criteria. 1. Progressive tumor is outside the original high-dose radiotherapy target volume as determined by the treating investigator, or 2. Histologic confirmation of tumor through biopsy or resection, or 3. Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than pseudoprogression or radiation necrosis obtained within 28 days of registration.
5. Patient must be at least 3 years of age.
6. Patient must weigh at least 10kg.
7. Patient must be able to swallow and retain orally administered medication. For patients unable to swallow capsules, oral ONC201 will be administered as a liquid formulation in Ora-Sweet.
8. From the projected start of scheduled study treatment, the following time periods must have elapsed from prior anti-cancer treatments: 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 anti-cancer antibodies (except 21 days for bevacizumab), or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.
9. Contrast-enhanced head CT or brain MRI within 21 days prior to start of study drug.
10. Adequate organ and marrow function as defined below: 1. Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to treatment (cycle 1 day 1, C1D1) 2. Hemoglobin >8.0 mg/dL without red blood cell transfusion ≤ 3 days prior to C1D1 3. Total serum bilirubin
Philadelphia, Pennsylvania, 19104