Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Everolimus; conventional surgery
Intervention description: Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week; Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: Male
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer; stage III prostate cancer

Summary:

      RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Giving everolimus before surgery may make the tumor smaller and
      reduce the amount of normal tissue that needs to be removed.

      PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus
      works in treating patients with newly diagnosed localized prostate cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed newly diagnosed, localized adenocarcinoma of
             the prostate, meeting any of the following criteria:

               -  Clinical stage T2a, T2b, T2c, or T3 disease (any grade or PSA)

               -  Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)

               -  Serum PSA ≥ 10 ng/dL (any grade or stage)

               -  Any stage, PSA, or Gleason score AND ≥ 35% chance of biochemical failure at 5
                  years based on Kattan's nomogram

          -  Recommended for radical prostatectomy

          -  Normal testosterone level

          -  No pure neuroendocrine or small cell prostate cancer

          -  No metastatic disease by CT scan, MRI, bone scan, or X-ray

          -  No clinical evidence of CNS metastases

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%

          -  ANC ≥ 1,500/μL

          -  Platelet count ≥ 100,000/μL

          -  Hemoglobin ≥ 8 g/dL

          -  AST and ALT ≤ 1.5 times upper limit of normal (ULN)

          -  Bilirubin ≤ 1.5 times ULN

          -  Creatinine ≤ 1.5 times ULN

          -  PT/PTT normal (no anticoagulants)

          -  No active unresolved infection

          -  No known HIV positivity

          -  Fertile patients must use effective contraception during and for 6 months after
             completion of study therapy

        Exclusion criteria:

          -  Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or
             temsirolimus) or to its excipients

          -  Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI
             function and alter the absorption of everolimus, including any of the following:

               -  Ulcerative disease

               -  Uncontrolled nausea

               -  Vomiting

               -  Diarrhea

               -  Malabsorption syndrome

          -  Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of
             therapy, except nonmelanoma skin cancer

          -  Uncontrolled concurrent illness including, but not limited to, any of the following:

               -  Ongoing or active infection (e.g., bacterial, viral or fungal)

               -  Severely impaired lung function

               -  Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)

               -  Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent
                  hepatitis)

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

          -  Psychiatric illness or social situation that would limit study compliance

          -  Any underlying medical condition which, in the principal investigator's opinion, will
             make the administration of everolimus hazardous OR obscure the interpretation of
             adverse events

        PRIOR CONCURRENT THERAPY:

          -  More than 4 weeks since major surgery

          -  More than 3 months since finasteride

          -  No prior or concurrent radiotherapy to the prostate gland or pelvis

          -  No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH
             antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or
             PC-SPES (or PC-x product) or estrogen-containing nutraceuticals

          -  No prior rapamycin mTOR inhibitor

          -  No prior small bowel resection that may significantly impair GI function and alter the
             absorption of everolimus

          -  No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy
             for prostate cancer

          -  No other concurrent investigational or commercial agents

          -  No other concurrent anticancer agents

          -  No concurrent, chronic treatment with systemic steroids (except inhaled or topical
             steroids) or another immunosuppressive agent

          -  No concurrent live vaccines

          -  No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as
             systemic therapy