Opaganib and Androgen Antagonists for the Treatment of Patients with Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria

• Patient must have mCRPC. Each patient must have: * Tissue diagnosis documented by pathology report, or clinic note attesting to same * Radiographically-demonstrated metastases * Patients must have adenocarcinoma, or ductal carcinoma, or combinations of these two entities
• Voluntary, signed and dated, Institutional Review Board (IRB)-approved informed consent form in accordance with regulatory and institutional guidelines
• Documented progression during treatment with enzalutamide or abiraterone, as determined by the enrolling investigator
• Testosterone level documented to be less than 50 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Bilirubin =< 1.5 times upper limit of normal (Common Terminology Criteria for Adverse Events [CTCAE] grade 1 baseline)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) & alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x upper limit of normal (ULN) (CTCAE grade 1 baseline)
• Subjects with Gilbert’s syndrome may be included if the total bilirubin is < 3 x ULN and the direct bilirubin is within normal limits
• Serum creatinine =< 1.5 x ULN (CTCAE grade 1 baseline)
• Absolute neutrophil count >= 1000 cells/mm^3
• Platelet count >= 75,000 (plt/mm^3) (CTCAE grade 1 baseline)
• Hemoglobin >= 9.0 g/dL
• Fasting blood glucose of < 165 mg/dL or random blood glucose of < 200 mg/dL
• Urinalysis: no clinically significant abnormalities
• International normalized ratio (INR) =< 1.7 for patients not on anti-coagulation medications (meds)
• Well-controlled blood pressure as determined by the treating investigator
• Patients requiring narcotic analgesics must be on stable doses for at least 2 weeks prior to study entry

Exclusion Criteria

• New York Heart Association class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
• Underlying psychiatric disorder requiring hospitalization within the last two years
• Clinically significant neurological disorder (Parkinson’s disease, dementia, multiple sclerosis), as determined by the enrolling investigator
• Active, uncontrolled bacterial, viral or fungal infection, requiring systemic therapy
• Treatment with radiation therapy, surgery, or investigational therapy within 28 days prior to registration
• Unwillingness or inability to comply with procedures required in this protocol
• Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator
• Patients who are receiving coumadin, apixaban, or rivaroxaban. Patients who are receiving other drugs that are sensitive substrates of CYP450 1A2, 3A4, 2B6, 2C8, 2C9, 2C19 or 2D6, P-gP, BCRP, and OATP1B1, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with opaganib may be treated on this study with careful monitoring for toxic effects or loss of efficacy of the relevant drug
• Patients who are currently participating in any other clinical trial of an investigational product
• Other primary malignancy requiring systemic treatment within past 5 years except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer
• Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator
• Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
• Patients that have had chemotherapy for castration resistant prostate cancer (patients can have had chemotherapy for castration sensitive PC) * Exception: Patients who had prior chemo for CRPC are eligible if they have a performance status (PS) = 0-1 and life expectancy of more than 6 months