A Phase II Safety and Efficacy Study With the VEGF Receptor Tyrosine Kinase Inhibitor GW786034 in Patients With Metastatic Urothelial Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 9
- 主要终点
- Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST])
研究概览
简要总结
This phase II trial is studying the side effects and how well pazopanib works in treating patients with metastatic urothelial cancer. 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.
详细描述
PRIMARY OBJECTIVES:
I. Assess the anti tumor activity and toxicity profile of pazopanib hydrochloride in patients with metastatic urothelial cancer.
SECONDARY OBJECTIVES:
I. Evaluate the pharmacokinetics of pazopanib hydrochloride in these patients. II. Evaluate pre- and post-treatment changes in circulating endothelial cells, monocytes and platelets, and angiogenesis-related factors in these patients.
OUTLINE: This is a multicenter study. Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed transitional cell cancer of the urothelium or bladder
- •Metastatic disease
- •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
- •No known brain metastases
- •ECOG performance status 0-2
- •Life expectancy ≥ 12 weeks
- •Platelet count ≥ 100,000/mm^3
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •PT/INR/PTT ≤ 1.2 times ULN
- •No proteinuria > 1+ on two consecutive dipsticks measured ≥ 1 week apart
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study
- •No condition that impairs the ability to swallow and retain pazopanib hydrochloride tablets, including any of the following:
- •Gastrointestinal tract disease resulting in an inability to take oral medication
- •Requirement for IV alimentation
- •Prior surgical procedures affecting absorption
- •Active peptic ulcer disease
- •No uncontrolled illness that would limit compliance with study therapy including, but not limited to, any of the following:
- •Ongoing or active infection
- •Psychiatric illness or social situations
- •No QTc prolongation (defined as a QTc interval ≥ 480 msecs) or other significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia)
- •No other conditions, including any of the following:
- •Serious or non-healing wound, ulcer, or bone fracture
- •Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- •Cerebrovascular accident within the past 6 months
- •Myocardial infarction, cardiac arrhythmia, or admission for unstable angina within the past 12 weeks
- •Venous thrombosis within the past 12 weeks
- •New York Heart Association (NYHA) class III or IV heart failure
- •Asymptomatic NYHA class II heart failure on treatment allowed
- •No other active second malignancy other than non-melanoma skin cancer
- •Patients are not considered to have an active malignancy if they have completed anti-cancer therapy and are considered by their physician to be ≤ 30% risk of relapse
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- •At least 4 weeks since prior radiotherapy
- •Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1 measurable and/or evaluable lesion(s) that has not been irradiated
- •At least 4 weeks since prior surgery
- •One prior chemotherapy regimen for metastatic urothelial or bladder cancer
- •More than 12 weeks since prior cardiac angioplasty or stenting
- •Prior adjuvant or neoadjuvant therapy allowed
- •No prior experimental treatment for metastatic disease
- •No other prior or concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent CYP2C9 substrates, including any of the following:
- •Anticoagulants (e.g., warfarin [therapeutic doses only])
- •Low molecular weight heparin and prophylactic low-dose warfarin (≤ 2 mg daily) allowed
- 另有 9 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive 800 mg oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pazopanib hydrochloride (Drug)
结局指标
主要结局
Best Tumor Response (Complete [CR] or Partial Response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST])
时间窗: Participants will be evaluated every 8 weeks during treatment and up to 1 year after completion of treatment.
Tumor response is defined as the total number of eligible patients whose disease has a complete or partial response to GW786034 according to the RECIST criteria. Per RECIST v1.0 criteria: A Complete Response (CR) requires the disappearance of all target lesions. A Partial Response (PR) requires \>=30% decrease in the sum of the longest diameter of target lesions from baseline measurement. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.
次要结局
- Confirmed Tumor Response (CR and PR)(Documented on 2 consecutive evaluations 8 weeks apart from the start of the treatment until disease progression/recurrence, assessed up to 1 year)
- Adverse Events Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0(Every 4 weeks during treatment (maximum duration was 44 weeks))
- Time to Disease Progression(Every 3 months from registration until progressive disease (PD), assessed up to 2 years after registration)
- Duration of Response(From the time an objective response is first noted to be either a CR or PR to the date progression is documented, assessed up to 1 year)
- Survival Time(Time from registration until death due to any cause, assessed every 6 months after PD for up to 2 years after registration)