Pazopanib Hydrochloride With or Without Bicalutamide in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
Condition: Hormone-Resistant Prostate Cancer; Recurrent Prostate Carcinoma
MeSH terms: Prostatic Neoplasms
Intervention: Bicalutamide; Laboratory Biomarker Analysis; Pazopanib Hydrochloride; Pharmacological Study
Intervention description: Given PO; Correlative studies; Given PO; Correlative studies
Intervention MeSH terms: Bicalutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying how well giving pazopanib with or without
      bicalutamide works in treating patients with prostate cancer that did not respond to hormone
      therapy. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth and by blocking blood flow to the tumor. Androgens can cause the growth of
      prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of
      androgens made by the body. Giving pazopanib hydrochloride together with bicalutamide may be
      an effective treatment for prostate cancer.
    

Eligibility criteria:

        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