Study of Abiraterone Acetate Plus ADT Versus APALUTAMIDE Versus Abiraterone and APALUTAMIDE in Patients With Advanced Prostate Cancer With Non-castrate Testosterone Levels

Inclusion Criteria: 1. Histologically confirmed prostate adenocarcinoma; 2. Hormone naïve patients with indication to ADT in the following settings: * Advanced loco-regional disease not amenable to curative local therapy (surgery or radiotherapy): T category T3/4 or node positive * Biochemical relapse after primary treatment (surgery or radiotherapy): patients in whom primary therapy is not appropriate or feasible with Previously treated with radical surgery and/or radiotherapy, now relapsing with at least one of the criteria: PSA \>= 4 ng/ml and rising with doubling time less than 10 months. or PSA \>= 20 ng/ml or N+ or M+ * Newly diagnosed metastatic disease: Tany Nany M+ 3. Patient is asymptomatic or moderately symptomatic regarding bone symptoms, i.e., no need for palliative radiation or radionuclide therapy; 4. Non-castration level of testosterone \> 230ng/dL (\> 8 nmol/L); 5. Baseline level of prostatespecific antigen (PSA) \> 2ng/dL; 6. ECOG performance status of 0 to 2; 7. Adequate hematologic, hepatic and renal function: 1. hemoglobin \> 10 g/dL, neutrophils \> 1.5×109 / L, platelets\> 100×109 / L; 2. total bilirubin \< 1.5x upper limit of normal (ULN); alanine (ALT) and aspartate (AST) aminotransferase \< 2.5 x ULN; 3. serum creatinine \< 1.5x ULN; potassium \> 3.5 mM; 8. No previous cancer (except treated basal-cell skin cancer); 9. Written informed consent obtained prior to any study procedure; 10. Men age 18 years and older; 11. Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant. Exclusion Criteria: 1. Prostate adenocarcinoma with neuroendocrine differentiation or small cell histology; 2. Biochemical recurrence without evidence of clinical or radiological disease; 3. Use of hormonal therapy or chemotherapy prior to randomization. Exception is courses of hormone therapy for localised disease must have been completed at least 12 months previously. It can have been given as adjuvant or neoadjuvant therapy. 4. Prior radiation therapy for a primary tumour within the 3 months before enrollment or for the treatment of metastases; 5. Known or suspected brain or skull metastases or leptomeningeal metastatic disease; 6. Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study; 7. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1 or currently enrolled in an investigational study; 8. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction; 9. Current or prior treatment with anti-epileptic medications for the treatment of seizures; 10. Impaired cardiac function, including any of the following: 1. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg); 2. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events or history of cardiac failure in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease; 3. Existing atrial fibrillation with or without pharmacotherapy. Other cardiac arrhythmia requiring pharmacotherapy; 4. History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect); 11. Specific underlying conditions for oral agents. For example: impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abiraterone or APALUTAMIDE (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) 12. General excluded medications (e.g., relevant to cytochrome P450 interactions) 1. Use of prescription drugs within 14 days prior to dosing or over-the-counter (OTC) medication within 7 days prior to dosing; 2. Consumption of grapefruit product or St John's wort within 7 days prior to dosing; 3. G-CSF, GM-CSF, erythropoietin, etc; 4. Coumadin; 5. Drugs which may cause QT prolongation; 6. Known sensitivity to drugs or metabolites from similar classes; 7. Known or suspected contraindications or hypersensitivity to APALUTAMIDE, bicalutamide or GnRH agonists or any of the components of the formulations; 13. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study.