Bicalutamide With or Without Everolimus 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 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.

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.