A First-in-human Phase I Single-agent Dose-escalation, Food Effect and Dose Expansion 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.
• 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, atypical teratoid/rhabdoid tumor, primary CNS embryonal/primitive neuroectodermal tumors, atypical and anaplastic meningiomas, choroid plexus tumors, and pineal region tumors.
• Patients must have recurrent and measurable disease as defined by RANO criteria, using either the HGG and/or low-grade glioma (LGG) RANO criteria based on tumor type, after having received established standard of care treatment for their disease and have no standard treatment options available as determined by the investigators.
• There is no limit on the number of total recurrences or prior therapies. However, prior therapies with known clinical benefit (including radiation) for specific tumor types are required. Karnofsky Performance Score (KPS) of greater than or equal to 70.
• 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
• 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.
• Patients must be fully vaccinated for coronavirus disease 2019 (COVID-19), as defined by the Center for Disease Control guidance for patients who are immunocompromised. Patients must have received required vaccination(s) by the time of signing consent and be considered fully immunized (typically 2 weeks after final vaccination) by the first dose of study drug (Cycle 1, Day 1).
• Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug (Cycle 1, Day 1).
• Patients must agree to follow study site requirements to limit transmission of COVID-19, such as wearing masks, social distancing, and maintaining good hand hygiene even after vaccination.