A Study of ONC201 for Refractory Meningioma

Inclusion Criteria: For both study arms: 1. Brain imaging demonstrating a meningioma for which resection has been recommended (Arm I) or any subject with pathologically proven meningioma without reasonable surgical options for complete resection, or reasonable radiation therapy options, determined by neurosurgery and radiation oncology opinions (Arm II) 2. Age \> 18 years old at time of study entry (consent) or adult male or female (For Nebraska, age of consent is ≥19 years old) 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 4. 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 \<1.5 X upper limit of normal (ULN), except in cases of Gilbert's disease 4. Aspartate aminotransferase (AST) (SGOT)/Alanine transaminase (ALT) (SGPT) ≤2 X ULN secondary to tumor 5. Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2) 5. Ability to understand and the willingness to sign a written informed consent document. 6. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception while on ONC201 and for at least 90 days after completion of treatment. Male subjects must be surgically sterile or must agree to use effective contraception while on ONC201 and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate. 7. Any number of prior medical therapies is allowed but not required. 8. Multifocal disease is allowed. 9. Subjects with history of neurofibromatosis may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months. For Arm II only: 10. Progression by Macdonald criteria: increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area). Progressive disease must based on scans done within 12 months or fewer of each other. 11. Subject must have no reasonable surgical or radiation therapy options, determined by neurosurgery and radiation oncology opinions. 12. Evidence of progressive disease at least 24 weeks after completion of radiation (external beam, interstitial brachytherapy, or radiosurgery). 13. Subject who elected to have partial tumor resection after confirmed progressive disease may still be considered, but radiographic measurable residual tumor(s) are required at baseline 14. Stable or decreasing steroid dose for two weeks. 15. Archival tissue must be available for correlative studies-a minimum of ten slides to be eligible, with up to 20 slides requested. Exclusion Criteria: 1. Participation in another clinical study with an investigational product during the last 28 days. 2. Active chemotherapy, including other investigational agents within 28 days of study treatment. 3. Craniotomy or other major surgery within 28 days of registration. 4. Evidence of metastatic meningiomas (as defined by extracranial meningiomas). 5. Known active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV). 6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. 7. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, or cerebrovascular accident. Subjects planning to continue on study after progression with the addition of bevacizumab cannot have uncontrolled hypertension, nephrotic syndrome, or had a history of intracranial bleeding or GI hemorrhage in the last 6 months. 8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the subject inappropriate for entry into the study. 9. Concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers. Subject must discontinue the drug for 14 days prior to registration. 10. Prolongation of QT/corrected QT interval by Fridericia (QT/QTcF) interval (QTc interval \>480 milliseconds) using Frederica's QT correction formula on two ECGs separated by at least 48 hours. 11. A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome. 12. Concomitant use of medication(s) known to prolong the QT/QTc interval.