Abiraterone Acetate Plus LHRH Agonist and Abiraterone Acetate Plus LHRH Agonist and Enzalutamide

Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (like the roll of dice) to 1 of 2 groups. You will have a 2 out of 3 chance of being assigned to Group A and a 1 out of 3 chance of being assigned to Group B. If you are in Group A, you will receive hormonal therapy (LHRH), abiraterone acetate, prednisone, and enzalutamide. If you are in Group B, you will receive LHRH, abiraterone acetate, and prednisone. Study Drug Administration: The study doctor will decide what hormone therapy you will receive, will explain when and how you should take it, and explain any risks. In addition, you will take 4 abiraterone acetate tablets by mouth each day (all at the same time) at least 1 hour before a meal or 2 hours after a meal. You will also take 1 tablet of prednisone by mouth 1 time each day to help lower the risk of side effects caused by abiraterone acetate. If you are in Group A, you will also take 4 capsules of enzalutamide by mouth each day. You should take enzalutamide at about the same time every morning. Enzalutamide can be taken with or without food. If you miss a dose, you should NOT take another dose until the next day. You should tell the study doctor as soon as possible if you miss a dose. About every 28-days is called a cycle. You should return all unused study drug and/or empty pill bottles at the end of each cycle. Study Visits: On Day 1 of Cycle 1: * You will have a physical exam. * Blood (about 3-4 tablespoons) will be drawn for routine tests and to check your prostatic specific antigen (PSA) level. On Day 15 of Cycles 1, 2 and 3, blood (about 2 tablespoons) will be drawn to check your liver function. These tests may be done at your local doctor's office and the results faxed to MD Anderson. On Day 1 of Cycles 2, 3, 4, 5 and 6: * You will have a physical exam. * Blood (about 3-4 tablespoons) will be drawn for routine tests. This blood will also be used to check your PSA level. The testing on Cycles 2, 4 and 6 may be done at your local doctor's office and the results faxed to MD Anderson. Within 14 days before surgery and at your End of Treatment Visit: * You will have a physical exam. * Blood (about 3-4 tablespoons) and urine will be collected for routine tests. This blood will also be used to check your PSA level, your blood sugar levels, and blood-clotting function. You will be asked to fast for at least 8 hours before these blood draws. * You will have a chest x-ray or a CT scan of the chest. * You will have an EKG to check your heart function. Surgery: After 6 cycles of study treatment, you will have surgery to remove your prostate. You will be asked to sign a separate consent form for this surgery, and the risks will be discussed with you. Your leftover prostate gland tissue from surgery will be collected and used for biomarker testing. About 4 to 8 weeks after your surgery: * You will have a physical exam. * Blood (about 3-4 tablespoons) drawn for routine tests. This blood will also be used to check your PSA, testosterone, cholesterol, and blood sugar levels. Length of Study: You may receive the study drugs for about 6 months. You will be taken off study early if the disease gets worse, if you have intolerable side effects, or if your study doctor thinks it is in your best interest to stop, or of you are unable to follow study directions. Your participation on the study will be over once you have completed the visits after surgery. This is an investigational study. Abiraterone acetate is FDA approved in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. Prednisone is FDA approved and commercially available as a corticosteroid. Enzalutamide is FDA approved and commercially available for the treatment of certain types of prostate cancer. Their combination with hormone therapy in patients with prostate cancer is investigational. Up to 69 patients will be enrolled in this study. All will be enrolled at MD Anderson.