A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 214
- 主要终点
- Progression-free Survival
研究概览
简要总结
This Phase II, multicenter, randomized, double-blind, placebo-controlled trial was designed to estimate the efficacy and characterize the safety of bevacizumab when combined with carboplatin + paclitaxel chemotherapy compared with carboplatin + paclitaxel chemotherapy alone in patients with previously untreated metastatic melanoma.
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
- Double (Participant, Investigator)
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
- •Signed Informed Consent Form
- •Age ≥ 18 years
- •Metastatic melanoma (Stage IV)
- •Histologically confirmed malignant melanoma with measurable or non-measurable disease
- •Ability and willingness to comply with study and follow-up procedures
排除标准
- •Prior treatment for Stage IV disease with chemotherapy or biologic therapy such as interferon and interleukin-2
- •Complete surgical resection or irradiation of all identifiable sites of disease at randomization
- •Radiation therapy within 14 days prior to Day 1
- •Prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial growth factor (VEGF) pathway-targeted therapy
- •Melanoma of ocular origin
- •Known central nervous system (CNS) disease/brain metastases (history of brain disease or active disease)
- •Life expectancy of < 12 weeks
- •Current, recent, or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- •Inadequate organ function
- •History of other malignancies within 5 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
- •Inadequately controlled hypertension
- •History of hypertensive crisis or hypertensive encephalopathy
- •New York Heart Association (NYHA) Class II or greater CHF
- •History of myocardial infarction or unstable angina within 6 months prior to Day 1
- •History of stroke or transient ischemic attack within 6 months prior to Day 1
- •Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
- •History of hemoptysis within 1 month prior to Day 1
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- •Serious, non-healing wound, active ulcer, or untreated bone fracture
- •Known hypersensitivity to any component of bevacizumab
- •Pregnancy (positive pregnancy test) or lactation
- •Current, ongoing treatment with full-dose warfarin
研究组 & 干预措施
Carboplatin+Paclitaxel+Placebo
干预措施: carboplatin (Drug)
Carboplatin+Paclitaxel+Placebo
干预措施: paclitaxel (Drug)
Carboplatin+Paclitaxel+Placebo
干预措施: placebo (Drug)
Carboplatin+Paclitaxel+Bevacizumab
干预措施: bevacizumab (Drug)
Carboplatin+Paclitaxel+Bevacizumab
干预措施: carboplatin (Drug)
Carboplatin+Paclitaxel+Bevacizumab
干预措施: paclitaxel (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: From randomization up to102 weeks. As of the clinical cut-off date (April 2009), the maximum time on treatment was 88 weeks, median time was 12.4 weeks for the Placebo arm and 16.1 weeks for the bevacizumab arm.
Progression-free survival (PFS) was defined as the time from randomization to documented disease progression (at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions) or death on study (death from any cause occurring no later than 30 days after last dose of any study treatment), whichever occurred first, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST). Median PFS was estimated using the Kaplan-Meier method.
次要结局
- Number of Participants With Objective Response(Up to 102 weeks)
- Duration of Objective Response(Up to 102 weeks)
- Overall Survival (OS)(Up to 102 weeks)
- Percentage of Participants With an Objective Response(Up to 102 weeks)
- Six-month Landmark Survival Rate(6 months)
- Twenty-Four Week Landmark Stable Disease(24 weeks)
- Number of Participants With Select Adverse Events(Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination.)