Inclusion Criteria:

- Histologically or cytologically confirmed prostate cancer

- Must have received prior hormonal therapy, including either medical (luteinizing
hormone-releasing hormone [LHRH] agonist) or surgical (orchiectomy) castration

- Castrate level of testosterone (< 50 ng/dL)

- Patients treated with LHRH agonists must continue or restart this therapy

- Must have radiological documentation of either measurable or non-measurable disease

- Must show documented progression of prostate cancer while on hormonal therapy as
indicated by PSA increase

- Rising PSA is defined as ≤ 2 consecutive rises in PSA taken ≥ 1 week and ≤ 2
months apart

- PSA ≥ 5 ng/mL

- No known brain metastases

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS
60-100%

- Life expectancy > 3 months

- White blood cell (WBC) ≥ 3,000/mm³

- Absolute neutrophil count (ANC) ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- International normalized ratio (INR) ≤ 1.2

- Activated partial thromboplastin time (PTT) ≤ 1.2 times upper limit of normal (ULN)

- Bilirubin normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times ULN

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Fertile patients must use effective contraception

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to pazopanib hydrochloride or bicalutamide

- Proteinuria ≤ 1+ on 2 consecutive dipsticks taken ≥ 1 week apart

- QTc < 480 msec

- No significant electrocardiogram (ECG) abnormalities

- No poorly controlled hypertension (systolic blood pressure [BP] > 150 mm Hg or
diastolic BP > 90 mm Hg)

- No condition (e.g., gastrointestinal [GI] tract disease resulting in an inability to
take oral medication or a requirement for intravenous (IV) alimentation; prior
surgical procedures affecting absorption; or active peptic ulcer disease) that
impairs the ability to swallow and retain pazopanib hydrochloride tablets

- No serious or nonhealing wound, ulcer, or bone fracture

- No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28
days

- No cerebrovascular accident within the past 6 months

- No myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac
angioplasty, or stenting within the past 12 weeks

- No venous thrombosis within the past 12 weeks

- No New York Heart Association (NYHA) class III-IV heart failure

- Patients with a history of NYHA class II heart failure who are asymptomatic on
treatment are eligible

- No concurrent uncontrolled illness, including, but not limited to, ongoing or active
infection

- No psychiatric illness or social situation that would preclude study compliance

- Recovered from all prior therapy

- Prior neoadjuvant or adjuvant chemotherapy allowed

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy

- At least 4 weeks since prior antiandrogens

- At least 4 weeks since prior surgery

- No prior bicalutamide therapy lasting > 3 months in duration

- Concurrent steroids allowed if no change in steroid dosage within the past 4 weeks

- No other concurrent investigational agents

- No concurrent therapeutic warfarin

- Concurrent low molecular weight heparin or prophylactic low-dose warfarin
allowed

- No concurrent combination antiretroviral therapy for human immunodeficiency virus
(HIV)-positive patients