A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate the Efficacy and Safety Of Bevacizumab, and Associated Biomarkers, In Combination With Paclitaxel Compared With Paclitaxel Plus Placebo as First-line Treatment Of Patients With Her2-Negative Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 481
- 试验地点
- 173
- 主要终点
- Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population
研究概览
简要总结
This is a Phase III, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of bevacizumab administered in combination with paclitaxel in patients with previously untreated, locally recurrent, or metastatic HER2-negative breast cancer. Patients will be randomized to one of two treatment arms: bevacizumab or placebo. All patients will be given an intravenous (IV) infusion of of paclitaxel (90 mg/m2) for 3 weeks during each 28-day cycle. bevacizumab or placebo (10 mg/kg) will be administered by IV infusion on Days 1 and 15 of each 28-day cycle. Patients will be treated until disease progression, unacceptable toxicity or death from any cause occurs.
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
- •Histologically or cytologically confirmed, HER2-negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- •ECOG performance status of 0 or 1
- •For women of childbearing potential, use of an acceptable and effective method of non-hormonal contraception
- •For patients who have received recent radiotherapy, recovery prior to randomization from any significant acute toxicity, and radiation treatments have to be completed more than 3 weeks from randomization
排除标准
- •Disease-Specific Exclusions:
- •HER2-positive status
- •Prior chemotherapy for locally recurrent or metastatic disease
- •Prior hormonal therapy < 2 weeks prior to randomization
- •Prior adjuvant or neo-adjuvant chemotherapy is allowed, provided its conclusion has been for at least 12 months prior to randomization
- •Investigational therapy within 28 days of randomization
- •General Medical Exclusions:
- •Life expectancy of < 12 weeks
- •Inadequate organ function
- •Uncontrolled serious medical or psychiatric illness
- •Active infection requiring intravenous (IV) antibiotics at screening
- •Pregnancy or lactation
- •History of other malignancies within 5 years prior to screening, except for tumors with a negligible risk for metastasis or death
研究组 & 干预措施
A
Paclitaxel + Bevacizumab [Avastin]
干预措施: Bevacizumab [Avastin] (Drug)
A
Paclitaxel + Bevacizumab [Avastin]
干预措施: Paclitaxel (Drug)
B
Paclitaxel + Placebo
干预措施: Paclitaxel (Drug)
B
Paclitaxel + Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population
时间窗: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Tumor assessment was performed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator. Disease progression was defined as at least 20 percent (%) increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm), unequivocal progression of existing non-target lesions, or presence of new lesions.
Progression Free Survival (PFS) in ITT Population
时间窗: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
PFS in High Baseline Plasma VEGF-A ITT Population
时间窗: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population
时间窗: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions.
次要结局
- Percentage of Participants Who Died - ITT Population(From randomization till death or clinical cut-off (up to 244 weeks))
- Percentage of Participants With an Objective Response - ITT Population(Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks))
- Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population(Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks))
- Overall Survival (OS) - ITT Population(From randomization till death or clinical cut-off (up to 244 weeks))
- Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population(1 year)
- Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population(From randomization till death or clinical cut-off (up to 244 weeks))
- OS - High Baseline Plasma VEGF-A ITT Population(From randomization till death or clinical cut-off (up to 244 weeks))
- Duration of Response - ITT Population(Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks))
- Percentage of Participants Who Were Alive at 1 Year - ITT Population(1 year)
- Duration of Response - High Baseline Plasma VEGF-A ITT Population(Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 111.3 weeks))