Pazopanib Hydrochloride With or Without Bicalutamide in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

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/mm\^3
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* 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, gastrointestinal (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