Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer

Inclusion Criteria:

• Age ≥ 18 years
• Participants must be able to care for themselves
• Adequate liver function
• Adequate kidney function
• Histologically confirmed diagnosis of adenocarcinoma of the prostate with biopsy within 90 days of enrollment
• High-risk prostate cancer
• No distant metastases as evaluated by a bone scan and CT of the pelvis (within 90 days of enrollment)
• Participants must have at least 4 biopsy cores containing prostate cancer with tissue available for histologic analysis
• Signed informed consent

Exclusion Criteria:

• Participants 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.)

• Prior pharmacologic androgen ablation for prostate cancer is not allowed including LHRH agonist therapy or oral anti-androgen therapy.

  o Previous use of either finasteride or dutasteride is allowed

• Participants, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, participants who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or participants that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 4 weeks

• Participants receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent.

  o Topical or inhaled corticosteroids are allowed.

• Participants should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
• Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin.

• Participants who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

  • Symptomatic congestive heart failure of New York heart Association Class III or IV
  • Uncontrolled cardiac arrhythmia
  • The use of anti-arrhythmic medications or implanted pacemakers or defibrillators is allowed and would not exclude a patient from enrollment.
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
  • Severely impaired lung function
  • Uncontrolled diabetes
  • Active (acute or chronic) or uncontrolled severe infections
  • Liver disease such as cirrhosis or severe hepatic impairment

• A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all participants.

  • Participants with previous documented history of Hepatitis B/C infection are excluded from enrollment.
  • Participants with high risk for hepatitis based upon medical history and risk factors must be screened for Hepatitis B and C, and if positive are excluded from enrollment.
• A known history of HIV seropositivity
• Participants with an active, bleeding diathesis
• Male patient whose sexual partner(s) are women of child bearing potential who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment

• Participants who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).

  o Sirolimus eluting coronary artery stents are allowed

• Participants with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
• Participants unwilling to or unable to comply with the protocol