Pazopanib Hydrochloride After Leuprolide Acetate or Goserelin Acetate in Treating Patients With Relapsed Prostate Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed prostate cancer

  • Stage D0
• Must have undergone some definitive local therapy for prostate cancer
• Must be free of macrometastatic disease, as evidenced by computed tomography (CT) scan and bone scan, if serum PSA ≥ 10 ng/mL prior to GnRH agonist therapy

• Progressive disease meeting the following criteria: NOTE: Patients who have undergone a prostatectomy and have two detectable, rising serum PSA levels are eligible

  • Two consecutive rises in PSA above nadir recorded after definite local therapy
  • Serum PSA concentrations must have absolute value of > 0.5 ng/mL (separated by ≥ 2 weeks) prior to beginning GnRH agonist therapy
• PSA < 0.5 ng/mL
• Testosterone < 30 ng/mL
• No measurable disease
• No brain metastases requiring steroid or anticonvulsant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60- 100%
• Prothrombin time (PT)/international normalization ratio (INR)/partial thromboplastin time (PTT) ≤ 1.2 times upper limit of normal (ULN)
• Bilirubin normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance > 50 mL/min
• Proteinuria ≤ 1+ on 2 consecutive dipsticks > 1 week apart
• Urine protein: creatinine ratio < 1 OR urine protein < 1.0 g/24 hours
• Fertile patients must use effective double-barrier contraception during study therapy OR completely abstain from sexual intercourse 14 days prior to, during, and for ≥ 21 days after completion of study therapy
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or to other agents used in the study

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Psychiatric illness or social situations that would preclude compliance with study requirements
• No human immunodeficiency virus (HIV) positivity

• No condition that impairs the ability to swallow and retain pazopanib hydrochloride tablets, including any of the following:

  • Gastrointestinal tract disease resulting in an inability to take oral medication
  • Requirement for intravenous (IV) alimentation
  • Prior surgical procedures affecting absorption
  • Active peptic ulcer disease

• No other conditions, including any of the following:

  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • Cerebrovascular accident within the past 6 months
  • Myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the past 6 months
  • Venous thrombosis within the past 12 weeks

  • New York Heart Association (NYHA) class III or IV heart failure

    • History of currently treated asymptomatic NYHA class II heart failure allowed

• Systolic blood pressure (BP) ≤ 140 mm Hg and diastolic BP ≤ 90 mm Hg

  • Prior initiation or adjustment of BP medication allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg
• More than 3 months since prior antiandrogen
• More than 4 months since prior orchiectomy or implantable luteinizing LHRH agonist

• No prior GnRH agonists except for neoadjuvant or adjuvant therapy associated with local therapy

  • Patients who have started a GnRH agonist for micrometastatic disease after local therapy allowed provided the following criteria are met:

    • Progressive disease
    • Willing to discontinue therapy before 6 months have elapsed
    • Have signed consent prior to completing 6 months of the initial hormone therapy
    • Are within 4 months of initiating GnRH agonist therapy
• No prior or concurrent GnRH antagonist therapy
• No concurrent ketoconazole

• No concurrent cytochrome P450 2C9 (CYP2C9) substrates, including any of the following:

  • Anticoagulants (e.g., warfarin [therapeutic doses only])

    • Low molecular weight heparin or prophylactic low-dose warfarin allowed
  • Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or nateglinide)
  • Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or methylergonovine)
  • Neuroleptics (e.g., pimozide)
  • Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)
  • Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexiletin, amiodarone, quinidine, or propafenone)
  • Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)
  • Miscellaneous medications (e.g., theophylline, quetiapine, risperidone, tacrine, clozapine, or atomoxetine)

• No concurrent medications associated with the risk of QTc prolongation and/or Torsades de Pointes

  • Replacement of drugs that do not carry these risks allowed
• No other concurrent non-Food and Drug Administration (FDA)-approved agents