Overview

This trial is active, not recruiting.

Conditions hormone-resistant prostate cancer, recurrent prostate carcinoma
Treatments bicalutamide, laboratory biomarker analysis, pazopanib hydrochloride, pharmacological study
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date September 2007
End date August 2015
Trial size 23 participants
Trial identifier NCT00486642, 7640, CDR0000549528, N01CM00032, N01CM62203, NCI-2009-00200, PHL-058, PMH-10036920, PMH-PHL-058

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive pazopanib hydrochloride PO QD on days 1-28. .
laboratory biomarker analysis
Correlative studies
pazopanib hydrochloride GW786034B
Given PO
pharmacological study
Correlative studies
(Experimental)
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.
bicalutamide BICALUTAMIDE
Given PO
laboratory biomarker analysis
Correlative studies
pazopanib hydrochloride GW786034B
Given PO
pharmacological study
Correlative studies

Primary Outcomes

Measure
PSA response rate
time frame: Up to 12 weeks

Secondary Outcomes

Measure
Median survival time
time frame: Up to 1 year after completion of treatment
Objective tumor response rate as assessed by RECIST criteria
time frame: Every 12 weeks during treatment and every 4 weeks for up to 12 weeks after completion of treatment
Progression-free survival
time frame: Time from start of treatment to time criteria are met for disease progression, assessed up to 12 weeks
Response duration
time frame: From the time measurement criteria are first met for complete response (CR) or partial response (PR) until the first date that recurrent disease is objectively documented, assessed up to 12 weeks
Stable disease rate as assessed by RECIST criteria
time frame: Measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, assessed up to 12 weeks
Survival rate
time frame: At 1 year
Time to disease progression
time frame: Time from start of treatment to time criteria are met for disease progression, assessed up to 12 weeks
Toxicity
time frame: During treatment and up to 12 weeks after completion of study treatment

Eligibility Criteria

Male participants at least 18 years old.

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

Additional Information

Official title A Phase 2 Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer
Principal investigator Kim Chi
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).