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.