A Phase 2 Study of GW786034 (Pazopanib) With or Without Bicalutamide in Hormone Refractory Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 6
- 主要终点
- PSA Response Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Arm A (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28.
.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28.
.
干预措施: Pazopanib Hydrochloride (Drug)
Arm A (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28.
.
干预措施: Pharmacological Study (Other)
Arm B (pazopanib hydrochloride, 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.
干预措施: Bicalutamide (Drug)
Arm B (pazopanib hydrochloride, 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.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (pazopanib hydrochloride, 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.
干预措施: Pazopanib Hydrochloride (Drug)
Arm B (pazopanib hydrochloride, 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.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
PSA Response Rate
时间窗: 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).
次要结局
- 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)
- 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)
- 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)
- Toxicity(Assessed up to 5 years)
- 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)
- Progression-free Survival(From time of treatment initiation to disease progression or death from any cause, whichever came first, assessed up to 5 years)