Adaptive Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate (the availability archival prostate tumor sample is preferred not required)
• Asymptomatic or minimally symptomatic (not requiring opioids for cancer related pain) metastatic castration-resistant prostate cancer (CRPC) patients on abiraterone as standard of care and achieved at least 50% decline of their pre-treatment PSA
• Performance status ECOG 0-2
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be < 2.5 x upper limit of normal (ULN)
• Total bilirubin < 1.5 x ULN
• Estimated creatinine clearance must be > 40 mL/min
• Absolute neutrophil count (ANC) > 1500/l
• Hemoglobin above 9 g/dl
• Platelet count > 100,000/l
• Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 28 days prior to study enrollment
• Prior surgical castration or concurrent use of gonadotropin-releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening < 50 ng/dL
• Ability to give written informed consent

Exclusion Criteria

• Except GnRH analogue therapy, any other therapies for prostate cancer (excluding bisphosphonate and denosumab) must be discontinued 3 weeks before the first dose of study drugs
• Prior treatments with Cyp 17 inhibitors like TAK-700/orteronel, ketoconazole, radium 223 or docetaxel (up to 6 cycles of docetaxel given in the non CRPC setting is allowed); prior treatment with sipuleucel-T is allowed
• Documented central nervous system metastases or liver metastasis
• Treatment with any investigational compound within 30 days prior to the first dose of study drugs
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy & have any evidence of residual disease; patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Uncontrolled hypertension despite appropriate medical therapy (blood pressure of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the screening period); Note: patients may be rescreened after adjustments of antihypertensive medications
• Unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade > 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.03), New York Association class III or IV heart failure
• Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C not contained with anti-viral therapy, life threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in investigator’s opinion, potentially interfere with participation in this study
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of study drugs, including difficulty swallowing tablets
• Subjects with delayed healing of wounds, ulcers, and/or bone fractures
• Inability to comply with protocol requirements