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

Phase 2

Completed

Conditions: Hormone-Resistant Prostate Cancer
Recurrent Prostate Carcinoma

Interventions: Other: Laboratory Biomarker Analysis
Drug: Bicalutamide
Drug: Pazopanib Hydrochloride
Other: Pharmacological Study

Registration Number: NCT00486642

Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 23

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (pazopanib hydrochloride)	Laboratory Biomarker Analysis	Patients receive pazopanib hydrochloride PO QD on days 1-28. .
Arm A (pazopanib hydrochloride)	Pazopanib Hydrochloride	Patients receive pazopanib hydrochloride PO QD on days 1-28. .
Arm B (pazopanib hydrochloride, bicalutamide)	Laboratory Biomarker Analysis	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.
Arm B (pazopanib hydrochloride, bicalutamide)	Pazopanib Hydrochloride	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.
Arm A (pazopanib hydrochloride)	Pharmacological Study	Patients receive pazopanib hydrochloride PO QD on days 1-28. .
Arm B (pazopanib hydrochloride, bicalutamide)	Pharmacological Study	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.
Arm B (pazopanib hydrochloride, bicalutamide)	Bicalutamide	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.

Primary Outcome Measures

Name	Time	Method
PSA Response Rate	Up to 12 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Median Duration of PSA-Response	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	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.
Stable Disease Rate as Assessed by RECIST Criteria	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	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 to Disease Progression	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	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.
Toxicity	Assessed up to 5 years	Patients who came off treatment due to toxicity.
Objective Tumor Response Rate as Assessed by RECIST Criteria	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	RECIST PR defined as - At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progression-free Survival	From time of treatment initiation to disease progression or death from any cause, whichever came first, assessed up to 5 years	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

Trial Locations

Locations (6): Ottawa Hospital and Cancer Center-General Campus
🇨🇦
Ottawa, Ontario, Canada
London Regional Cancer Program
🇨🇦
London, Ontario, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
BCCA-Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
University Health Network-Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada