Inclusion
Absolute neutrophil count (ANC) ≥1,500/mcL.
Platelets ≥100,000/mcL.
Hemoglobin ≥9.0 mg/dL without transfusion in 2 prior weeks.
Total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with Gilbert's syndrome may be included with total bilirubin \>1.5 × ULN if direct bilirubin is ≤1.5 × ULN).
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × ULN.
Measured or estimated creatinine clearance (CLcr) ≥40 mL/minute for patients with creatinine levels above normal. CLcr will be calculated by the Cockcroft-Gault equation for renal function. 10. (Inclusion Criterion #10 was removed in Amendment 3) 11. Patients must provide a tumor specimen (paraffin-embedded block and/or frozen tissue) from a prior resection or biopsy available that is sufficient to perform biomarker assays, ≥15 unstained slides for immunohistochemistry (IHC) analysis must be received by the NOB by the first dose of study drug (Cycle 1, Day 1). For patients with ≥10 to \<15 slides, eligibility will be reviewed on a case-by-case basis. 12. Dependent upon dose level assignment and drug formulation (i.e., capsules versus powder in bottle \[PIB\]), patients must be able to either swallow oral capsules or swallow liquids. 13. Patients must provide study-specific informed consent prior to enrollment. No Durable Power of Attorney or Next of Kin can provide initial consent. 14. Patients must be able to tolerate a magnetic resonance imaging (MRI) study with intravenous gadolinium contrast. 15. (Inclusion Criterion #15 was removed in Amendment 6) 16. Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug (Cycle 1, Day 1). Patients who had documented COVID-19 infection within 90 days of treatment but more than 20 days from infection do not need to be tested. 17. (Inclusion Criterion #17 was removed in Amendment 6)
Exclusion
Corrected QT interval (QTc) ≥470 msec on screening electrocardiogram (ECG; using the QTc by Fridericia's \[QTcF\] formula);
Angina pectoris that requires the use of anti-anginal medication;
Ventricular arrhythmias except for benign premature ventricular contractions;
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
Conduction abnormality requiring a pacemaker;
Valvular disease with documented compromise in cardiac function; and/or
Symptomatic pericarditis. 7. Patients with a history of cardiac dysfunction including any of the following:
Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction function;
History of documented congestive heart failure (New York Heart Association functional classification III-IV); and/or
Documented cardiomyopathy. 8. Patients who have had an ischemic or hemorrhagic stroke in the last 3 months. If the patient has had a recent tumor resection, cerebral ischemic or hemorrhagic changes that occur peri operatively are not an exclusion. 9. Patients with refractory epilepsy are excluded. Patients with primarily or secondarily generalized seizures in the 28 days prior to study enrollment will be excluded. Peri-operative seizures, defined as seizures occurring within the 7 days after a stereotactic biopsy, open biopsy, or surgical resection will not be an exclusion as long as the patient has had no generalized seizures starting 8 days after the surgical procedure. Patients with prior seizures must be on stable doses of 1 or 2 seizure medications for at least 14 days prior to study enrollment. 10. Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ONC206 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 11. Patients who have been treated with any hematopoietic colony-stimulating growth factors (CSFs) (e.g., granulocyte-CSF, granulocyte-macrophage-CSF) ≤2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued. 12. Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin derivative anticoagulant. 13. Patients who are taking strong inhibitors or inducers of cytochrome P450 (CYP) 3A4, 2D6, 1A2, 2C9, and 2C19 within at least 14 days prior to the first dose of study drug (Cycle 1, Day 1); these medications are excluded throughout the study. 14. Women who are pregnant or breast feeding. 15. Women of child-bearing potential with a positive serum pregnancy test ≤72 hours prior to the first dose of study drug (Cycle 1, Day 1). 16. Patients who are receiving concomitant standard and/or investigational anti-cancer therapy. 17. Patients with alcohol or substance abuse which, in the opinion of the Investigator, would interfere with compliance or safety. 18. Patients with the presence of any other serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with patients' safety, obtaining informed consent or compliance to the study procedures as determined by the Investigators. 19. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, or men who do not agree to use highly effective contraception during treatment and for 16 additional weeks after the final dose of study drug.
True abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Sterilization: Females must have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.
If patients are not practicing true abstinence and/or if the patient or sexual partner have not had a sterilization procedure as listed above, patients and their sexual partners must follow double barrier contraception in accordance with the guidelines for contraception below:
Females of childbearing potential:
Must use an intrauterine device or intrauterine system, during dosing of any study agent and for 16 weeks after final dose of study drug; or
Must use a double barrier method of contraception: use of an occlusive cap (diaphragm or cervical/vault cap) with spermicide for women combined with use of a condom by their male partners capable of conceiving offspring.
Males capable of conceiving offspring must use condoms during dosing of study agent and for an additional 16 weeks after final dose of study drug.