Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Everolimus, lupron, bicalutamide, and radiation
Intervention description: Everolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1.
Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks).
Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy.
Lupron injections will begin on study day 15 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections.
Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study.
Intervention MeSH terms: Everolimus; Leuprolide; Bicalutamide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate; Cancer; Everolimus; Radiation

Summary:

      The purposes of this study are to:

        -  Determine the safest and highest dose of the study drug RAD001 (Everolimus) that can be
           taken in combination with hormonal and radiation therapy in men with high risk prostate
           cancer.

        -  Evaluate changes in patient reported quality of life

        -  Evaluate biomarkers from prostate tumor samples. Biomarkers are various traits which can
           be used to identify the progress of a disease or condition, which can help researchers
           determine the effect the study treatment has on the tumor. Biomarkers can also help
           determine areas for further research.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Participants must be able to care for themselves

          -  Adequate 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, targeted 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

          -  Any previous therapeutic radiation therapy to the pelvis.

          -  Known gastrointestinal dysfunction or an inability to take oral medications that would
             preclude taking an oral medication.

          -  Prior treatment with any investigational drug within the preceding 4 weeks of
             registration

          -  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 registration 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

          -  Uncontrolled diabetes mellitus despite adequate therapy. Patients with a known history
             of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood
             glucose and antidiabetic treatment must be monitored closely throughout the trial and
             adjusted as necessary;

          -  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