Bicalutamide With or Without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients
Condition: Cancer of Prostate
MeSH terms: Prostatic Neoplasms; Overweight; Recurrence
Intervention: Observation and Bicalutamide; Metformin and Bicalutamide
Intervention description: Cycles 1 - 2: Observation without treatment Cycles 3 - 8: Bicalutamide 50 mg daily, orally, continuously to the end of study (week 32).; Cycles 1-2: Metformin 1000mg BID Cycles 3-8: Bicalutamide 50 mg daily and Metformin 1000 mg BID
Intervention MeSH terms: Metformin; Bicalutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Obesity and metabolic syndrome are prevalent among prostate cancer patients. Having an
      elevated insulin level in the blood is associated with a shorter median time to cancer
      progression and median overall survival in patients with an elevated PSA after prior
      treatment. Androgen deprivation therapy (ADT) with drugs like bicalutamide is frequently used
      in this patient population,with no proven benefit, which may increase mortality and
      morbidity.This study evaluates how metformin in combination with bicalutamide affects
      prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        Ability to understand and the willingness to sign a written informed consent

        Male 18 years or older

        Histologically or cytologically confirmed diagnosis of prostate cancer

        Patient must have had previous treatment with definitive surgery or radiation therapy or
        cryoablation

        Patient may have prior salvage therapy (surgery, radiation or other local ablative
        procedures) within 6 months prior to randomization if the intent was for cure.Prophylactic
        radiotherapy to prevent gynecomastia within 4 weeks prior to randomization is allowed BMI >
        25 at study entry

        Patient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines or
        experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSADT were
        documented after the testosterone level was > 150ng/dL.

        Patient must have hormone-sensitive prostate cancer as evident by a serum total
        testosterone level > 150 ng/dL within 12 weeks prior to randomization.

        PSA must be < 30 ng/mL at study entry

        Patient may not have had therapy modulating testosterone levels (such as luteinizing
        hormone,releasing-hormone agonists/antagonists and antiandrogens) within 1 year prior to
        randomization, unless it was in the neoadjuvant and/or adjuvant setting

        Patient must have evidence of biochemical failure after primary therapy and subsequent
        progression. Biochemical failure is declared when the PSA reaches a threshold value after
        primary treatment and it differs for radical prostatectomy or radiation therapy.

          1. For radical prostatectomy the threshold for this study is PSA ≥ 0.2ng/mL

          2. For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA
             achieved post radiation with or without hormone therapy (2006 RTOG-ASTRO Consensus
             definition).

          3. PSA progression requires a PSA rise above the threshold measured at any time point
             since the threshold was reached.

        PSA doubling time between 3 and 9 months. PSA calculation requires two consecutive PSA
        rises (PSA2 and PSA3) above the threshold PSA (total 3 PSA values); PSA2 and PSA3 must be
        obtained within 12 months of study entry. All baseline PSAs should be obtained at the same
        reference lab. Patient's PSA doubling time must be calculated using the following formula
        (http://www.mskcc.org/nomograms/prostate/psa doubling-time):

        ECOG performance status less than or equal to 2

        Ability to swallow the study drugs

        Subjects must have normal organ and marrow function as defined below:

          1. Absolute neutrophil count greater than or equal to 1,000/mL

          2. Hemoglobin greater than or equal to 10 g/dL

          3. Platelets greater than or equal to 100,000/mL

          4. Total bilirubin within normal institutional limits

          5. AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional ULN

          6. Creatinine clearance greater than or equal to 60 mL/min/1.73 m2

          7. Hgb A1c ≤ 6.5

        Exclusion Criteria:

        Evidence of metastatic disease on imaging studies (CT and/or bone scan)

        Diagnosis of diabetes mellitus defined as

          1. Fasting blood glucose > 126 mg/dl or,

          2. Random blood glucose > 200 mg/dl

          3. Hemoglobin A1C > 6.5%

        Need for treatment with any conventional modality for prostate cancer (surgery, radiation
        therapy, and hormonal therapy)

        Prior hormonal therapy for recurrent prostate cancer (hormonal therapy given in a
        neoadjuvant or adjuvant setting and greater than 6 months before entry is acceptable)

        Treatment within the last 30 days with any investigational drug

        Radiation therapy within prior 6 months (prophylactic radiotherapy to prevent gynecomastia
        within 4 weeks prior to randomization is allowed)

        Known hypersensitivity to metformin

        Prior history of lactic acidosis

        Any history of myocardial infarction in the past 12 months

        Subjects who consume more than 3 alcoholic beverages per day Subjects with serious
        intercurrent illness, including, but not limited to, ongoing or active infection,
        symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
        other nonmalignant medical or psychiatric illness that is uncontrolled or whose control may
        be jeopardized by the complications of this therapy or may limit compliance with the study
        requirements (at the discretion of the investigator)

        Patient with previous or concurrent malignancy. Exceptions are made for patients who meet
        any of the following conditions: Basal cell or squamous cell carcinoma of the skin or prior
        malignancy that has been adequately treated and patient has been continuously disease free
        for ≥ 2 years.

        Subjects currently treated with metformin and/or bicalutamide or who have been treated with
        metformin and/or bicalutamide in the past 6 months.

        Subjects who have taken 5a-reductase inhibitors (finasteride or dutasteride), saw palmetto,
        or PC-SPES within the last 6 weeks are ineligible. Subjects will be eligible for the study
        after the wash out period of 6 weeks.