Once-daily Oral Seviteronel in Patients With Castration-Resistant Prostate Cancer Progressing on Enzalutamide or Abiraterone.

Inclusion Criteria

• Subjects must be ≥18 years of age.
• Subjects or their legal representatives must be able to provide written informed consent.
• Subjects must have documented histological or cytological evidence of adenocarcinoma of the prostate.
• Subjects must have an ECOG Performance Score of 0-1.
• Subjects must have undergone orchiectomy, or have ongoing LHRH analogue therapy prior to drug initiation. Subjects on LHRH analogues must remain on these agents for the duration of the study.
• Subjects must have castrate levels of testosterone (≤50 ng/dl [1.7 nmol/L]) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values ≥1 week between each assessment. The PSA value at the Screening visit must be ≥2ng/mL with or without:
• Soft tissue disease progression defined by RECIST 1.1 at Screening or ≤ 28 days of C1D1. Measurable disease is not required for entry. Lymph nodes ≥ 1.5cm (short axis) are considered measurable disease (PCWG3)
• Bone disease progression defined by ≥2 new lesions on bone scan at Screening, or ≤28 days of C1D1
• Subjects must have received abiraterone and/or enzalutamide. Subject must have received either abiraterone or enzalutamide for ≥12 weeks. Other second generation CYP17 inhibitors/androgen receptor antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place of enzalutamide.
• Subjects must have adequate hematopoietic function as evidenced by:
• WBC ≥3,000/µl
• ANC ≥1,500/µl
• Platelet count ≥100,000/µl
• HGB ≥10 g/dl and not transfusion dependent
• Subjects must have adequate liver function, including all of the following:
• Total serum bilirubin ≤2.0 x ULN unless the subject has documented Gilbert syndrome;
• Aspartate and alanine aminotransferase (AST & ALT) ≤3.0 x ULN or ≤5.0 x ULN if subject has liver metastasis;
• Alkaline phosphatase ≤2.0 x ULN or ≤5 x ULN in case of bone metastasis and/or hepatic metastasis
• Subjects must have adequate renal function as evidenced by a serum creatinine of <2.0 mg/dl.
• Subjects must have potassium (K+) >3.5 mEq/l.
• Subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting a Screening and continuing throughout the study period and for 3 months after final study drug administration • Two acceptable forms of birth control include:
• Condom (barrier method of contraception), and 2. One of the following:
• Oral, injected or implanted hormonal contraception
• Placement of an intrauterine device (IUD) or intrauterine system (ISU)
• Additional barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Vasectomy or surgical castration ≥ 6 months prior to Screening. 13. Subjects able to swallow study medication 14. Subjects able to comply with study requirements

Exclusion Criteria

• Subjects who have completed sipuleucel-T (Provenge ®) treatment within 28 days of study drug initiation.
• Subjects on 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or dutasteride (AVODART®) within 28 days of study drug initiation.
• Subjects who received any investigational agent ≤28 days of study drug initiation.
• Subjects who received palliative radiotherapy ≤2 weeks of study drug initiation.
• Subjects with symptomatic CNS metastases.
• Subjects with a history of another invasive malignancy ≤3 years of study drug initiation.
• Subjects with a QTcF interval of >470 msec; if the Screening ECG QTcF interval is >470 msec, it may be repeated, and if repeat <470 msec, the subject may be enrolled.
• Subject with clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second degree or third degree atrioventricular heart block without a permanent pacemaker in place)
• Subject that started a bone modifying agent (e.g. bisphosphonates, denosumab) ≤ 28 days of study drug initiation (note: ongoing bone modifying agents administered > 28 days are allowed).
• Subject with any medical condition that could preclude subject participation in the study, pose an undue medical hazard, or which could interfere with study results.
• Subject with Class III or IV Congestive Heart Failure as defined by the New York Heart Association (NYHA) functional classification system within the previous 6 months.
• Subject with a history of loss of consciousness or transient ischemic attack ≤ 12 months of study drug initiation.
• Subject with known active HIV, Hepatitis B, or Hepatitis C infections.
• Subject with known or suspected hypersensitivity to seviteronel, or any components of the formulation
• Subject with any other condition which in the opinion of the investigator would preclude participation in the study.