Phase II Trial of Pazopanib (GW786034) in Pre-Treated and Untreated Metastatic Melanoma Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 4
- 主要终点
- Tumor Response Rate
研究概览
简要总结
This phase II trial is studying the side effects of pazopanib hydrochloride and to see how well it works in treating patients with metastatic melanoma that cannot be removed by surgery. Pazopanib hydrochloride 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. To assess the anti-tumor activity and safety profile of single agent Pazopanib (pazopanib hydrochloride).
SECONDARY OBJECTIVES:
I. To assess the impact of Pazopanib on circulating levels of vascular endothelial growth factor (VEGF).
II. To examine the association between tumor response and B-Raf and N-Ras mutations.
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 confirmed unresectable malignant melanoma
- •Radiographic or clinical evidence of metastatic disease
- •Measurable disease with ≥ 1 lesion whose longest diameter can be measured as ≥ 2.0 cm by CT or MRI scans or ≥ 1.0 cm by spiral CT scan
- •Disease that is measurable by physical examination only is not allowed
- •No known intraluminal metastatic lesion(s) with suspected bleeding
- •No brain metastases by MRI or CT scan
- •ECOG performance status 0-2
- •Life expectancy > 12 weeks
- •WBC ≥ 3,000/μL
- •Hemoglobin ≥ 9 g/dL
- •Absolute neutrophil count ≥ 1,500/μL
- •Platelets ≥ 100,000/μL
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine ≤ 1.5 times ULN
- •Serum troponin normal
- •Urine protein ≤ 1+ (≤ 30 mg/dL) on 2 consecutive dipstick or other urine assessments taken ≥ 1 week apart
- •QTc interval < 480 msec
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia)
- •No serious nonhealing wound, ulcer, or bone fracture
- •No history of abdominal fistula, gastrointestinal perforation, active diverticulitis, intra-abdominal abscess, or gastrointestinal tract bleeding within the past 28 days
- •No history of myocardial infarction, cardiac arrhythmia within the past 6 months
- •No NYHA class III-IV heart failure
- •Patients with a history of class II heart failure and who are asymptomatic on treatment may be eligible
- •No history of bleeding disorder, including hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
- •No uncontrolled infection
- •No evidence of active bleeding or bleeding diathesis
- •No hemoptysis within 6 weeks of first dose of study drug
- •No active peptic ulcer disease
- •No inflammatory bowel disease
- •No ulcerative colitis or other gastrointestinal conditions with increased risk of perforation
- •No history of cerebrovascular accident, including transient ischemic attack, pulmonary embolism, or untreated deep venous thrombosis within the past 6 months
- •Patients with recent deep vein thrombosis who have been treated with therapeutic anticoagulating agents within the past 6 weeks are eligible
- •No known endobronchial lesions or involvement of large pulmonary vessels by tumor
- •No current active hepatic or biliary disease, except Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease
- •No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg and diastolic BP > 90 mm Hg)
- •No condition that impairs ability to swallow and retain pazopanib hydrochloride (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
- •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 uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonably be expected to limit compliance with study requirements
- •No admission for unstable angina, cardiac angioplasty, or stenting within the past 6 months
- •More than 6 weeks since prior major surgery
- •More than 4 weeks since prior and no concurrent radiotherapy
- •At least 14 days or 5 half-lives and no concurrent CYP interactive medications
- •No prior radiotherapy to ≥ 25% of bone marrow
- •No prior therapy with a VEGFR tyrosine-kinase inhibitor
- •No concurrent antiretroviral therapy for HIV-positive patients
- •No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride
- 另有 4 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pazopanib Hydrochloride (Drug)
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Tumor Response Rate
时间窗: Up to 5 years
Tumor response rate is defined as the number of eligible patients whose disease status meets the Response Evaluation Criteria In Solid Tumors (RECIST) criteria for compete response (CR) or partial response (PR) divided by the number of evaluable patients. A ninety percent confidence interval for the true response proportion will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution and using the Duffy-Santner approach. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the largest dimension (LD) of target lesions taking as reference the baseline sum LD.
Toxicity
时间窗: Up to 5 years
Toxicity is defined as any grade 3 or higher adverse event as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and at least possibly related to treatment. The maximum grade for each type of toxicity will be recorded for each patient. We report the number of patients experiencing a grade 3 or higher adverse event at least possibly related to treatment.
次要结局
- Overall Survival(From registration to death due to any cause, assessed up to 5 years)
- Progression Free Survival(From registration to documentation of disease progression, assessed up to 5 years)
- Duration of Response(From time of documented response to the date progression is documented, assessed up to 5 years.)