PRIMARY OBJECTIVES:~I. To estimate the overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC) who have SATISFACTORY features after to 8 weeks of maximal androgen receptor (AR)-inhibitory therapy and receive treatment with abiraterone acetate, prednisone and apalutamide plus or minus ipilimumab.~II. To estimate the OS of men with mCRPC who have UNSATISFACTORY features after to up to 8 weeks of maximal androgen receptor (AR)-inhibitory therapy and receive treatment with abiraterone acetate, prednisone, apalutamide, cabazitaxel and carboplatin.~III. To determine the TOXICITY PROFILE of the following combinations in men with mCRPC:~IIIa. Abiraterone acetate, prednisone, apalutamide. IIIb. Abiraterone acetate, prednisone, apalutamide and ipilimumab. IIIc. Abiraterone acetate, prednisone, apalutamide, cabazitaxel and carboplatin.~IV. To determine whether the BASELINE AR RESPONSE SIGNATURE correlates with SATISFACTORY or UNSATISFACTORY features after up to 8-weeks of treatment with abiraterone, prednisone and apalutamide.~SECONDARY OBJECTIVES:~I. To pick the winner in terms of time to treatment failure (TTF) between the following two combinations, in men with mCRPC and satisfactory features after 8 weeks of maximal AR-inhibitory therapy:~Ia. Abiraterone acetate, prednisone, apalutamide. Ib. Abiraterone acetate, prednisone, apalutamide and ipilimumab. II. To determine the TTF in men with mCRPC and unsatisfactory features after up to 8 weeks of maximal AR-inhibitory therapy ted with abiraterone acetate, prednisone, apalutamide, cabazitaxel and carboplatin.~III. To determine whether the baseline AR response signature predicts for benefit by prognostic grouping (satisfactory/unsatisfactory) and treatment arm.~IV. To investigate therapy-specific marker signatures (immune based, bone based and anaplastic) and their link to outcome.~V. To collect and archive bone marrow biopsy, bone marrow aspirate, serum, plasma, and tissue samples in study patients for later hypothesis generating associations.~OUTLINE: After an 8-week lead-in phase, patients with satisfactory decline in serum markers are randomized to 1 of 2 arms (Arm 2A or 2B), and patients with unsatisfactory decline in serum markers are assigned to Arm 3.~LEAD-IN PHASE: Patients receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and apalutamide PO daily for 8 weeks in the absence of disease progression or unexpected toxicity.~ARM 2A: Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily in the absence of disease progression or unexpected toxicity.~ARM 2B: Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive ipilimumab intravenously (IV) over 90 minutes on day 1 of courses 4-7. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.~ARM 3: Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1 of courses 4-13. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.~After completion of study treatment, patients are followed up at 14 and 30 days, and then every 6 months thereafter.
This randomized phase II trial studies the side effects and how well abiraterone acetate, prednisone, and apalutamide work with or without ipilimumab or cabazitaxel and carboplatin in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Drugs, such as abiraterone acetate and apalutamide may lessen the amount of androgens made by the body. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as prednisone, cabazitaxel, and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving abiraterone acetate, prednisone, and apalutamide with or without ipilimumab or cabazitaxel and carboplatin may be a better way to treat patients with castration-resistant prostate cancer that has spread to other places in the body.