It is hypothesized that treatment with cisplatin will reverse emerging refractoriness to enzalutimide in patients with CRPC by affecting AR function.

Inclusion Criteria:

• Histologic diagnosis of prostate cancer
• Age 18 yrs or older
• Able to provide written, informed consent
• Subjects who have received docetaxel for metastatic disease are eligible if absolute neutrophil count is greater than 100 and platelet count is greater than 100,000 and their bone marrow reserve is deemed to be adequate
• Subjects with castration resistant prostate cancer, as defined by having testosterone level of less than 50 Nano gram/dl, being treated with enzalutamide with a rise in PSA, confirmed with a repeat measurement within 1 to four weeks, or asymptomatic radiographic progression

Exclusion Criteria:

• Subjects with estimated glomerular filtration rate of less than 50 ml/min
• Subjects with hearing impairment. The treating physician may decide which subjects should not receive cisplatin based on audiometry or based on clinical judgment.
• Subjects with grade 2 or greater neuropathy
• Subjects who in the opinion of the treating physician could not tolerate the standard hydration before receiving cisplatin
• Chemotherapy naïve subjects who in the opinion of the treating physician should receive docetaxel instead of enrolling on the trial and receive cisplatin