RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistance (The RESTORE Study)

The trial will enroll up to 110 patients, 30 for each Cohorts A-C and 20 for Cohort D. Eligible patients will continue on androgen ablative therapy with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) if not surgically castrated to suppress endogenous testosterone production. Patients will also receive intramuscular injection with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dosing scheme was designed to produce rapidly fluctuating serum testosterone levels from the supraphysiologic to the near-castrate range (i.e. Bipolar Androgen Therapy \[BAT\]). Assessments for response to testosterone will be made approximately every 3 months. Upon displaying evidence of progression, patients will then go on to receive either abiraterone (Cohort B) or enzalutamide (Cohort A), whichever agent they had previously progressed on prior to study enrollment. Patients in Cohort C will remain on LHRH agonist therapy and receive no additional androgen ablative hormonal therapy while those in the mutation-positive Cohort D will receive enzalutamide regardless of prior therapy.