A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same doses of abiraterone and steroids they were receiving prior to study entry and will be randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with abiraterone. Once the best regimen is established in Part A, based on safety and antitumor activity, patients will be randomized to the selected treatment regimen and dose of AT13387 in combination with abiraterone or AT13387 alone in Part B (Phase 2).

Inclusion:

1. Must have prostate cancer
2. Have received prior castration by orchiectomy and/or hormone therapy
3. Males >18 years of age
4. Normal activity level for self care
5. Have been receiving abiraterone therapy with a steroid for ≥1 month
6. Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression
7. Have adequate bone marrow, liver and kidney function
8. Must be willing to provide pre-existing tumor samples, if this material exists. If pre-existing samples are not available, a sample must be obtained during screening
9. Must be willing and able to provide written informed consent and comply with the protocol and study procedures

Exclusion:

1. Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or histone deacetylase (HDAC) inhibitor compound
2. Have received chemotherapy within 4 weeks prior to receiving study drug
3. Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug
4. Hypersensitivity to AT13387 or other components of the drug product
5. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug
6. Severe systemic diseases or active uncontrolled infections
7. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
8. Abnormal heart function
9. Other cancer except for adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder cancer, or other cancer from which the subject has been disease-free for at least 3 years;
10. No known brain or CNS involvement
11. Unable to receive corticosteroids or history of pituitary or adrenal dysfunction
12. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus