Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
The primary objective of this phase 1 trial is to determine the maximum tolerated dose (MTD),
 food effect, safety and tolerability of oral ONC206 in patients with recurrent, primary CNS
 neoplasms.
Inclusion Criteria:

 -  Age ≥ 18 years with a recurrent, primary CNS neoplasm. Primary CNS neoplasms included
 in this study: glioblastoma and glioblastoma histologic subtypes, gliosarcoma, primary
 CNS sarcomas, anaplastic glial neoplasms including anaplastic astrocytoma, anaplastic
 oligodendroglioma, anaplastic mixed neuronal-glial tumors, and pilocytic astrocytoma
 with anaplastic features, diffuse astrocytoma, oligodendroglioma, gliomatosis cerebri,
 pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, diffuse
 midline gliomas and histone mutated gliomas, ependymoma, anaplastic ependymoma, and
 all ependymoma subtypes, medulloblastoma and all medulloblastoma subtypes, ATRT,
 primary CNS embryonal/primitive neuroectodermal tumors, atypical and anaplastic
 meningiomas, choroid plexus tumors, and pineal region tumors.

 -  Advanced disease after having received established standard of care treatment for
 their disease and have no standard treatment options available

 -  Karnofsky Performance Score (KPS) of greater than or equal to 70.

 -  Measurable or evaluable disease defined by RANO criteria. The exception will be
 patients who have had surgery in the past 4 weeks, patients who are post-operative
 after a maximal resection will be allowed to enroll after 4 weeks from surgical
 resection.

 -  Washout for prior investigational or approved cytotoxic chemotherapy is 28 days prior
 to the first dose of ONC206; 42 days in the case of nitrosoureas; 28 days or 5
 half-lives (whichever is less; but not less than 14 days) in case of investigational
 or approved molecularly targeted agent; 14 days in the case of radiotherapy.

 -  Patients will be required to enroll on the NCI Neuro-Oncology Branch natural history
 study (16-C-0151).

 -  No major surgery in the prior 4 weeks

 -  Patients must have normal organ and marrow function as defined below:

 -  An available tumor specimen (paraffin-embedded block and/or frozen tissue) from prior
 resection or biopsy, ≥15 unstained slides for IHC analysis.

 -  Ability to swallow oral capsules.

 -  Ability to tolerate an MRI study with intravenous gadolinium contrast.

 -  Men and women must use double barrier contraceptives

 Exclusion Criteria:

 -  Prior bevacizumab for treatment of high-grade glioma

 -  Known HIV-positive test on combination antiretroviral therapy

 -  Active cardiac disease

 -  Ischemic or hemorrhagic stroke in last 3 months

 -  Refractory epilepsy and patients with primary or secondarily generalized seizures in
 the 28 days before enrollment are excluded. Peri-operative seizures occurring within 7
 days of surgery with resolution by day 8 after surgery are allowable. Patients must be
 on stable doses of one or two seizure medications for 14 days prior to study
 enrollment.

 -  Impairment of gastrointestinal (GI) function

 -  Concurrent use of warfarin sodium or other Coumadin-derivative anti-coagulants

 -  Concurrent use of strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 are
 excluded at least 14 days prior to and throughout the study.