Prostate Cancer Study In Men Who Have Failed First-Line Androgen Deprivation Therapy
Condition: Neoplasms, Prostate
MeSH terms: Prostatic Neoplasms
Intervention: dutasteride; placebo; bicalutamide
Intervention description: 0.5mg dutasteride (Investigation Product); making placebo; 50 mg Casodex or generic equivalent
Intervention MeSH terms: Bicalutamide; Dutasteride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 127.0
Sex: Male
Minimum age: 40 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: prostate cancer; androgen deprivation therapy

Summary:

      Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT) the male
      hormone that leads to benign prostate growth. By blocking the conversion of testosterone to
      DHT, dutasteride could allow bicalutamide to be a more effective anti-androgen thus
      prolonging bicalutamide's efficacy.
    

Eligibility criteria:

        Inclusion criteria:

          -  Men ≥40 and ≤90 years of age

          -  Must have asymptomatic prostate cancer that has progressed during androgen deprivation
             therapy (rising PSA). PSA progression must have occurred after first-line treatment
             with GnRH analogues ( e.g. leuprolide, goserelin) or orchiectomy. PSA progression is
             defined by three rises in PSA each measured at least 4 weeks apart within the previous
             year.

          -  Serum PSA ≥2 and ≤20ng/ml from central laboratory. One PSA retest from central
             laboratory is allowed if the value is <2 or >20ng/ml; or if the PSA value is not
             consistent with the previous rising PSA values that determined progression while on a
             GnRH analogue.

          -  Serum Testosterone <50ng/ml from central laboratory.

          -  Non-metastatic prostate cancer as confirmed on prior bone scan performed within 8
             weeks of screening.

          -  Expected survival ≥ 2 years

          -  ECOG Performance status 0, 1, or 2

        Exclusion criteria:

          -  Additional hormonal therapy (excluding the current use of a GnRH analogue) within the
             past 6 months of:

          -  Estrogens (e.g. megestrol, medroxyprogesterone, cyproterone, DES)

          -  Drugs with antiandrogenic properties (e.g., spironolactone if >50mg/day, flutamide,
             bicalutamide*, ketoconazole**, progestational agents)

             *The use of an antiandrogen during GnRH analogue induction for <6 weeks is acceptable,
             but none within the 3 months prior to study entry.

             **The use of topical ketoconazole is permitted prior to and during the study. NOTE:
             Use of dietary and herbal supplements (e.g., selenium, Vitamin E, saw palmetto),
             excluding daily vitamins, during the study is discouraged, but not prohibited. All
             dietary and herbal supplement usage will be recorded in the eCRF.

          -  Treatment with oral glucocorticoids during the 3 months prior to randomization or
             expectation of their use during the study.

          -  Prior chemotherapy for prostate cancer. (prior prostatectomy or radiotherapy to the
             prostate are allowed)

          -  Prostate surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon
             dilatation, prosthesis, and cryosurgical ablation within 2 months prior to enrollment.

          -  Current and/or previous use of the following medications:

          -  Finasteride (Proscar, Propecia), or Dutasteride (GI198745, AVODART) exposure within 6
             months prior to study entry

          -  Anabolic steroids (within 6 months prior to study entry)

          -  Participation in any investigational or marketed drug trial within the 30 days prior
             to the first dose of study drug or anytime during the study period.

          -  Any unstable serious co-existing medical condition(s) including but not limited to
             myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias,
             clinically evident congestive heart failure, or cerebrovascular accident within 6
             months prior to Screening visit; uncontrolled diabetes; or peptic ulcer disease which
             is uncontrolled by medical management.

          -  Abnormal liver function test greater than 1.5 times the upper limit of normal for
             alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase
             [ALP] or bilirubin.

          -  Serum creatinine >2.0 times the upper limit of normal.

          -  History of another malignancy within five years that could affect the treatment of
             prostate cancer or survival of the subject.

          -  History or current evidence of drug or alcohol abuse within the last 12 months.

          -  History of any illness (including psychiatric) that, in the opinion of the
             investigator, might confound the results of the study or pose additional risk to the
             subject.

          -  Known hypersensitivity to any 5 alpha-reductase inhibitor or to any drug chemically
             related to dutasteride.