Prostate Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven diagnosis of adenocarcinoma of the prostate

  • Metastatic (M1) disease as evidenced by soft tissue and/or bony metastases at the time of initiation of androgen-deprivation therapy (ADT)

  • Must have at least one of the following:

    • Visceral disease (liver, lung, other viscera)
    • Bone metastases to sites in either the axial (spine, pelvis, ribs, or skull) and/or the appendicular (clavicle, humerus, or femur) skeleton
    • Distant lymph node disease (e.g., above the aortic bifurcation, etc.)
  • No small cell or neuroendocrine prostate cancer

• Patients must be receiving ADT (e.g., gonadotropin-releasing hormone (GNRH) antagonist, with or without antiandrogen) prior to entering this study

  • Degarelix, a FDA-approved is an acceptable form of ADT

• Suboptimal response to ADT induction as defined by the following criteria:

  • Declining PSA (current PSA is less than the PSA prior to starting ADT) that fails to reach 4 ng/mL or below despite continuous ADT

    • PSA of > 4 ng/mL must be observed between 6-9 months after the initiation of ADT
    • No patients with a rising PSA
  • No patients with radiographic progression when compared to available imaging studies performed prior to starting the GNRH agonist/antagonist therapy
• Patients who have measurable disease must have radiographic assessment (at least an abdominal/pelvic CT scan) within 28 days prior to registration
• Non-measurable disease must be assessed (i.e., bone scan) within 42 days prior to registration

• No patients with a history of brain metastases or who currently have treated or untreated brain metastases

  • Patients with clinical evidence of brain metastases must have a brain CT scan or MRI negative for metastatic disease within 56 days prior to registration

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 10 g/dL
• Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min
• Bilirubin ≤ 1.5 times ULN (unless documented Gilbert disease)
• AST and ALT < 2.5 times ULN
• Potassium ≥ 3.5 mmol/L
• Albumin > 3.5 g/dL
• Patient must have a testosterone value of < 50 ng/dL obtained within 28 days prior to registration

• Patients must have controlled blood pressure defined as systolic blood pressure < 160 mm Hg and diastolic blood pressure < 95 mm Hg

  • Patients with a history of hypertension are eligible provided blood pressure is controlled by anti-hypertensive treatment
• Patients who have partners of child-bearing potential must be willing to use a method of birth control with adequate barrier protection during the study and for 13 weeks after the last study drug administration
• Must be able to take oral medication without crushing, dissolving, or chewing tablets

• No other prior malignancy is allowed except for any of the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • Adequately treated stage I or II cancer from which the patient is currently in complete remission
  • Any other cancer from which the patient has been disease-free for 5 years

• No patients with active or symptomatic viral hepatitis or chronic liver disease

  • No moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment

• No history of NYHA class III or IV heart failure

  • Patients must have LVEF ≥ 50%

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 2 years since prior neoadjuvant or adjuvant gonadotropin-releasing hormone (GNRH) agonist/antagonist therapy (related to previous surgery or radiation)

  • Prior enrollment to SWOG-S0925 (either arm) is not exclusionary, as long as appropriate wash-out periods are observed
• At least 6 weeks since prior and no concurrent finasteride or dutasteride
• At least 28 days since prior radiotherapy or surgery and recovered
• At least 14 days since prior investigational products

• At least 4 weeks since prior flutamide (6 weeks for bicalutamide and nilutamide) with no evidence of a falling PSA

  • No other concurrent oral antiandrogen
• No prior or concurrent cytotoxic chemotherapy or radiopharmaceuticals for prostate cancer
• No prior or concurrent ketoconazole for the treatment of prostate cancer
• Not requiring more than 10 mg a day of prednisone for another medical indication
• Not planning to receive any concurrent cytotoxic chemotherapy, immunotherapy, surgery, or radiotherapy during protocol treatment
• No concurrent hormonal-acting agents, including diethylstilbestrol/DES, aldosterone, PC-SPES, or spironolactone
• No concurrent antifungal medication (e.g., fluconazole or itraconazole)
• No medications that alter cardiac conduction