Phase I/II Combined Biological Therapy of Breast Cancer Using Monoclonal Antibodies Directed Against HER2/Neu Proto-Oncogene and Vascular Endothelial Growth Factor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 36
- 主要终点
- To establish the maximum tolerated dose (MTD) or recommended phase II dose of rhuMAb VEGF (bevacizumab) administered intravenously every 14 days to patients with HER2-amplified relapsed or metastatic breast cancer receiving concomitant Herceptin therapy
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of combined treatment with trastuzumab (Herceptin) and bevacizumab (anti-VEGF antibody) in patients with HER2-positive metastatic breast cancer.
详细描述
Based on preclinical experiments conducted in our laboratories, we hypothesize that the aggressive behavior of HER2-overexpressing breast cancers is due in part to increased angiogenesis resulting from HER2-induced increases in vascular endothelial growth factor (VEGF) expression. In vivo experiments suggest that combined blockade of the HER2 receptor and VEGF results in superior anti-tumor efficacy compared with either treatment alone.
The current clinical trial, for which the phase I portion has been completed, will examine the efficacy and safety of trastuzumab (Herceptin) and bevacizumab (anti-VEGF antibody) in the treatment of HER2-overexpressing metastatic breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Metastatic or relapsed locally advanced breast cancer
- •HER2-positive by FISH
- •No prior chemotherapy for metastatic disease
- •ECOG performance status 0-2
- •Normal left ventricular ejection fraction
- •Bidimensionally measurable disease
- •Oxygen saturation > 90% on room air
排除标准
- •Other invasive malignancy within 5 years
- •More than 3 different metastatic sites
- •>50% liver involvement by metastasis
- •Newly diagnosed untreated Stage IIIB breast cancer
- •Prior chemotherapy for metastatic disease
- •Clinically significant cardiovascular disease
- •History or evidence of CNS disease
- •Major surgery within 28 days prior to day 0
- •Current or recent use of parenteral anticoagulants
- •WBC < 3,000/uL
- •Platelet count < 75,000/uL
- •Hemoglobin < 9.0 g/dL
- •Total Bilirubin > 2.0 mg/dL
- •AST or ALT > 5 time upper limit of normal for subjects with documented liver metastases; > 2.5 times upper limit of normal for subjects without evidence of liver metastases
- •Proteinuria (> 1g protein/24 hours at baseline)
- •Prior therapy with Herceptin or rhuMAb VEGF (bevacizumab)
结局指标
主要结局
To establish the maximum tolerated dose (MTD) or recommended phase II dose of rhuMAb VEGF (bevacizumab) administered intravenously every 14 days to patients with HER2-amplified relapsed or metastatic breast cancer receiving concomitant Herceptin therapy
次要结局
- To evaluate the clinical safety and toxicities of rhuMAb VEGF when administered in combination with Herceptin
- To characterize the pharmacokinetics of rhuMAb VEGF and Herceptin given in combination
- To evaluate the efficacy of rhuMAb VEGF plus Herceptin in terms of clinical activity when administered as an intravenous infusion, in patients with previously untreated metastatic or relapsed breast cancer