Dutasteride in Treating Patients With Prostate Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer, meeting all of the following criteria:

  • Prostate-specific antigen (PSA) < 10.0 ng/mL
  • T1c-T2a disease
  • Gleason sum of 6 or 7 (secondary pattern 4 only)

• Patients with low risk disease must meet the following criteria:

  • Gleason pattern 3 + 3
  • PSA < 10.0 ng/mL
  • Clinical T2a disease
• Patients with Gleason secondary pattern 4 (i.e., Gleason Pattern 3 + 4) are eligible but must not have a primary pattern 4, PSA > 10 ng/mL, or clinical T2b disease
• Measurable disease on MRI of at least 0.2 cc, based on planimetry volume

• Biopsy-proven disease within 2 years of screening visit

  • No biopsy artifact on MRI scan (minimum 12-week interval between biopsy and baseline MRI)
• Eligible for active surveillance according to the criteria set out by the National Institute for Health and Clinical Excellence

PATIENT CHARACTERISTICS:

• ALT and AST ≤ 2 times the upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2 times ULN
• Bilirubin ≤ 1.5 times ULN
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min
• Able to swallow and retain oral medication
• Able and willing to participate in the study for its duration
• Able to read and write (health-outcomes questionnaires are written)
• Able to understand instructions related to study procedures and give written informed consent
• No history of another malignancy within five years that could affect the diagnosis of prostate cancer
• No history or current evidence of drug or alcohol abuse within the last 12 months that might confound the results of the study or pose additional risk to the patient
• No known hypersensitivity to any 5α-reductase inhibitor or to any drug chemically related to dutasteride

• No contraindication for undergoing gadolinium-enhanced MRI, including any of the following:

  • Inability to see tumor focus of ≥ 0.2 cc on T2 sequences
  • Previous allergic reaction to gadolinium
  • Serum creatinine > ULN
  • Incompatible pacemaker
  • Metal fragments in eyes
  • Hip replacements that give artifact with prostate/pelvis views
  • Any artifact or condition that reduces image quality of MRI (e.g., inability to keep still)

• No unstable serious co-existing medical condition(s) including, but not limited, to any of the following:

  • 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
  • Peptic ulcer disease uncontrolled by medical management

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy (external-beam or brachytherapy), high-intensity focused ultrasound (HIFU), or photodynamic therapy (PDT)
• No prior chemotherapy
• At least 3 months since prior and no concurrent prostatic surgery, including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation

• No prior oral glucocorticoids

  • Glucocorticoids, except inhaled or topical, are not permitted within 3 months prior to visit one
• No prior GnRH analogues (e.g., leuprolide, goserelin)
• No prior or concurrent hormonal treatment (e.g., megestrol, medroxyprogesterone, cyproterone, DES) of prostate cancer

• No current and/or prior use of the following medications:

  • Finasteride (Proscar, Propecia), or dutasteride (GI198745, AVODART) exposure within 12 months prior to study entry
  • Any other investigational 5α-reductase inhibitors within the past 12 months
  • Anabolic steroids within the past 6 months

  • Drugs with antiandrogenic properties within the past 6 months (e.g., spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, progestational agents)

    • The use of cimetidine is permitted prior to study entry
    • The use of topical ketoconazole is permitted prior to and during the study
• No participation in another investigational or marketed drug trial within the 30 days prior to the first dose of study drug or anytime during the study period