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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada
London Regional Cancer Program
London, Ontario, Canada
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
PSA Response Rate
Prostate-specific antigen (PSA) response rate (defined as a confirmed \> / = 50% decline (minimum 5ng/ml) in PSA from baseline maintained for \>4 weeks, and without other evidence of disease progression documented at time of confirmatory values).
Time frame: Up to 12 weeks
Objective Tumor Response Rate as Assessed by RECIST Criteria
RECIST PR defined as - At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Time from start of treatment to time criteria are met for disease progression or death from any cause, whichever came first, assessed up to 5 years
Progression-free Survival
PFS is defined as the time from treatment initiation to disease progression or death from any cause, whichever came first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From time of treatment initiation to disease progression or death from any cause, whichever came first, assessed up to 5 years
Median Duration of PSA-Response
Definition of PSA response: \>= 50% fall (minimum 5 ng/ml) in PSA from baseline maintained for \>4 weeks, and without other evidence of disease progression documented at time of confirmatory values. PSA response duration will commence on the date of the first \>=50% decline in PSA. The response duration ends when PSA progression criteria are met with the second increasing PSA value. PSA progression in PSA responders: rise in PSA of 50% (minimum 5ng/ml) above nadir value and confirmed by a second increasing value at least 1 week later.
Time frame: From time PSA response criteria are met until time PSA progression criteria are met or death from any cause, whichever came first, up to 5 years
Stable Disease Rate as Assessed by RECIST Criteria
RECIST Stable defined as - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Measured from the start of the treatment until the criteria for progression are met or death from any cause, whichever came first, assessed up to 5 years
Time to Disease Progression
Earliest date on which disease progression was determined by any of the methods listed: PSA progression, objective disease progression (Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) or cancer-related symptomatic progression.
Time frame: Time from start of treatment to time criteria are met for disease progression or death from any cause, whichever came first, assessed up to 5 years
Toxicity
Patients who came off treatment due to toxicity.
Time frame: Assessed up to 5 years
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