Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer

Inclusion Criteria: KEY POINTS: 1. Adenocarcinoma of the prostate confirmed histologically. 2. Metastatic disease confirmed by biopsy or imaging studies. 3. Castrate-resistant prostate cancer (i.e., progression of prostate cancer while receiving standard androgen ablation therapy, orchiectomy or luteinizing hormone-releasing hormone \[LHRH\] antagonist). Castrate levels of serum testosterone must be documented at progression in patients who have not had an orchiectomy. 4. Chemotherapy-naive or previously treated with docetaxel for metastatic prostate cancer. 5. ECOG of 0 to 2. 6. Patients must have progressive metastatic prostate cancer by at least 1 of the following criteria: * Progression of measurable lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Bone progression defined by 2 or more new lesions on bone scan. * PSA progression is determined by a minimum of two rising PSA levels with an interval of 1 week or greater between each determination. The screening PSA measurement (documenting progression) must be greater than or equal to 2 ng/mL. 7. Adequate hematologic, hepatic and renal function. 8. Adequate coagulation parameters and serum chemistries. 9. Ability to swallow and retain oral medication. 10. Life expectancy of 6 months or greater. 11. Ability to understand the nature of the study and give written informed consent. Exclusion Criteria: 1. Treatment with more than 2 prior chemotherapy regimens. 2. Previous treatment with enzalutamide or other investigational androgen receptor inhibitors. 3. Previous treatment with PI3K/mTOR inhibitors. 4. Known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or its excipients. 5. Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of study drug is required. 6. Most recent chemotherapy ≤21 days from first dose of study treatment and/or patient did not recover from most recent chemotherapy side effects prior to study entry. 7. CNS metastases.