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Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms

Trial Status: Active

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.

Maryland

Bethesda
National Institutes of Health Clinical Center
Status: ACTIVE
Contact: Mark R. Gilbert
Phone: 240-760-7126

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Chimerix

  • Primary ID ONC206-01
  • Secondary IDs NCI-2021-03639, NIH 20C0069
  • Clinicaltrials.gov ID NCT04541082