This phase II clinical trial will explore the efficacy of rapidly cycling non-cross reactive
      treatment therapies in the treatment of patients with newly diagnosed mCRPC. The primary
      hypothesis is that the best chance of eliminating or controlling disease is when the cancer
      is treatment naïve, and has not yet developed therapeutic resistance. By finding an optimal
      drug deployment strategy of already approved and available treatments for mCRPC, the
      researchers believe providers can more effectively treat an intrinsically heterogeneous
      disease, delay/prevent drug resistance, as well as minimize treatment toxicity.

      All of the treatment agents selected have well-defined individual toxicity profiles from
      large phase III trials, but there is limited clinical data about the toxicity profiles of
      these drugs in combinations. While each agent is generally well tolerated, toxicities remain
      a significant concern given the older age of the typical mCRPC patient, the comorbid
      conditions common to this patient population, as well as those borne from previous chronic
      androgen deprivation therapy.

      Each drug in the proposed treatment regimen will be used at their FDA-approved dosing and
      indication, with the exception of cabazitaxel, which will be used prior to disease
      demonstration of docetaxel failure, and in combination with carboplatin. The proposed
      sequencing is rationally designed, and based on each drug's distinct mechanisms of action as
      well as their toxicity profiles.

      The rapidly-cycling treatment regimen contains three, separate, consecutive treatment
      modules, each lasting 3 months: 1. Abiraterone; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide
      + Radium-223. Therapeutic agents are delivered as non-cross reactive combinations, in order
      to achieve optimal therapeutic dosing at each cycle and decrease possibility of significant
      adverse effects.

      To the researcher knowledge, no study has evaluated the use of rapidly cycling, non-cross
      reactive therapies for the treatment of mCRPC. The hypothesis is that the identification of
      optimal combinations and sequencing of rapidly cycling non-cross reactive therapies can help
      prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.

      Primary objective is to evaluate the time to disease progression after completion of all
      modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Secondary
      objectives are to evaluate overall survival, prostate-specific antigen (PSA) response rate
      with each treatment module, changes to alkaline phosphatase level, and assess safety of the
      rapidly-cycling, non-cross reactive regimen. Additional exploratory objective are to evaluate
      the correlation of a peripheral whole-blood RNA signature with clinical outcome measures
      during and after treatment, and to evaluate changes to AR-V7 expression in CTCs with
      different treatment modalities and clinical outcomes.