Bicalutamide With or Without Everolimus in Treating Patients With Recurrent or Metastatic Prostate Cancer (UCDCC#215)

• Progression-free survival [ Time Frame: Time between registration and disease progression or death ] [ Designated as safety issue: No ]
• Time to treatment failure [ Time Frame: until discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: Study participants will be followed for rest of life ] [ Designated as safety issue: No ]

• Progression-free survival [ Designated as safety issue: No ]
• Time to treatment failure [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Toxicity rates as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying bicalutamide and everolimus to see how well they work compared with bicalutamide in treating patients with recurrent or metastatic prostate cancer.

OBJECTIVES:

• To compare the PSA response rate in patients with hormone-independent recurrent or metastatic adenocarcinoma of the prostate treated with bicalutamide and everolimus after first-line androgen deprivation therapy.
• To evaluate the time to treatment failure and overall survival of these patients.
• To assess the toxicity of bicalutamide and everolimus in these patients.

OUTLINE: Patients are stratified according to disease status (metastatic disease vs biochemical recurrence without measurable disease). Patients are randomized to 1 of 2 treatment arms.

Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 28-42 days and then every 3 months thereafter.

• Drug: bicalutamide
  Bicalutamide 50 mg oral daily
  Other Name: Casodex
• Drug: Everolimus
  RAD001 10 mg oral capsule daily - continuously. Patients will be on this study continuously until disease progression, development of side effects, or patient request
  Other Name: Afinitor

Inclusion Criteria

1. Participants must be adult males >18 years.
2. Patients must have histologically or cytologically confirmed CaP with a Gleason score available or interpretable.
3. Patients must have CaP deemed to be androgen independent.
4. Measurable disease is not required.
5. Patients must have been surgically or medically castrated. If the method of castration was LHRH agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists. Serum testosterone must be at castrate levels (< 50 ng/dL) within 3 months prior to registration.
6. Participant has not been on any previous therapy with androgen receptor antagonists or mTOR inhibitors. Note: patients who have taken an androgen receptor antagonist for a brief period (no more than 2 months) at the start of LHRH agonist therapy to prevent flare will be considered eligible.
7. Men enrolled in this trial must agree to use adequate contraception prior to study entry and for the duration of study participation.
8. Patients must have normal organ and marrow function.
9. Ability to understand and the willingness to sign a written informed consent document
10. ECOG performance status 0-2.
11. Patients having any respiratory symptoms such as cough and shortness of breath have undergone pulmonary function testing revealing no worse than mild impairment.

Exclusion Criteria

1. No documented histological confirmation of CaP.
2. Patient has received other hormonal therapy besides first-line androgen deprivation therapy with LHRH agonist, LHRH antagonist, orchiectomy, high-dose steroid, abiraterone, provenge and ketoconazole.
3. Patients who have received prior treatment with an mTOR inhibitor.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with RAD001.
6. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
7. Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
8. Prior treatment with any investigational drug within the preceding 4 weeks.
9. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent.
10. Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
11. Patients on herbs or other alternative medicines for the treatment of prostate cancer, including but not limited to saw palmetto, PC-SPES.
12. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
13. Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin or other Stage 0 or I cancers.
14. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001.
15. Patients with an active, bleeding diathesis.
16. History of noncompliance to medical regimens.
17. Patients unwilling to or unable to comply with the protocol.
18. Patients with active pulmonary disorders or history of moderately to severely impaired pulmonary function tests will be excluded from the study.
19. Patients with symptomatic metastatic prostate cancer such as moderate to severe pain, impaired organ function or spinal cord compression will be excluded from this study unless these issues have been taken care of.