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

 I. To determine the therapeutic activity of GW786034 (pazopanib hydrochloride) with and
 without bicalutamide in the treatment of hormone-refractory prostate cancer using prostate
 specific antigen (PSA)-response rate.

 SECONDARY OBJECTIVES:

 I. To estimate objective tumor response in patients with measurable disease. II. To estimate
 the median time to progression. III. To investigate the safety and tolerability of GW786034
 with and without bicalutamide.

 IV. To estimate the median duration of PSA-response. V. To determine the steady state levels
 of GW786034 with and without bicalutamide.

 VI. To investigate the correlation between prior exposure to bicalutamide and non-steroidal
 anti-androgens with response and survival outcomes.

 OUTLINE: Patients are randomized to 1 of 2 treatment arms.

 ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28.

 ARM II: Patients receive pazopanib hydrochloride PO QD on days 1-28. Patients also receive
 bicalutamide PO QD on days 8-28 of course 1 and on days 1-28 in all subsequent courses.

 Courses in both arms repeat every 28 days in the absence of disease progression or
 unacceptable toxicity.

 After completion of study treatment, patients are followed up every 4 weeks for 12 weeks.
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