LHRH analog, Abiraterone, and Prednisone in Treating Patients with Stage IV Castration Sensitive Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• > 75% PSA decline after 12 to 16 weeks of run in period with LHRH, and AR directed therapy
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
• 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
• Ability to give written informed consent

Exclusion Criteria

• Prior LHRH analog with LHRH analogue for non-metastatic prostate cancer within 12 months prior to study enrollment; or > 3 months of LHRH analog in the metastatic setting
• Prior treatments with TAK-700/Orteronel, ketoconazole, abiraterone, darolutamide, apalutamide or enzalutamide for more than 12 weeks
• Documented central nervous system metastases or liver metastasis
• Prior surgical castration
• Requiring opioids for cancer related pain
• 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 and 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 100 mmHg diastolic 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 5.0), 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 tables
• Subjects with delayed healing of wounds, ulcers, and/or bone fractures
• Inability to comply with protocol requirements