A Phase I-II Study of Lapatinib and Docetaxel as Neoadjuvant Treatment for HER-2 Positive Locally Advanced/Inflammatory or Large Operable Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 129
- 试验地点
- 15
- 主要终点
- Phase I part: Dose limiting toxicity during cycle 1
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as docetaxel, fluorouracil, epirubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving trastuzumab after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of docetaxel and lapatinib when given with or without combination chemotherapy and to see how well they work in treating women with locally advanced, inflammatory, or resectable breast cancer.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of neoadjuvant therapy comprising docetaxel and lapatinib ditosylate before or after fluorouracil, epirubicin hydrochloride, and cyclophosphamide (FEC chemotherapy) in patients with HER2-positive locally advanced, inflammatory, or large resectable breast cancer. (Phase I)
- Determine the safety of this regimen in these patients. (Phase I)
- Determine the pathological complete response rate in patients treated with neoadjuvant docetaxel and lapatinib ditosylate followed by FEC chemotherapy, and with neoadjuvant docetaxel and trastuzumab (Herceptin®) followed by FEC chemotherapy. (Phase II)
Secondary
- Determine the biological activity (i.e., changes in apoptosis and proliferation markers [PTEN mutation and function, pAkt, mTOR, and associated proteins]) of neoadjuvant docetaxel and lapatinib ditosylate in these patients. (Phase I)
- Determine adverse events or biological modifications. (Phase I)
- Determine the tolerability of these regimens in these patients. (Phase II)
- Determine the clinical activity of these regimens. (Phase II)
- Identify genes that may predict response in patients treated with docetaxel and lapatinib ditosylate. (Phase II)
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
arm 1
干预措施: docetaxel+lapatinib (Drug)
arm 2
干预措施: docetaxel + trastuzumab (Drug)
arm 3
干预措施: docetaxel + trastuzumab + lapatinib (Drug)
结局指标
主要结局
Phase I part: Dose limiting toxicity during cycle 1
时间窗: during study
Phase II: Pathological complete response rate
时间窗: end of study
次要结局
- Phase I: Changes in apoptosis and proliferation markers.(end of Phase I)
- Phase II: Tolerability, clinical/radiological response rates, breast conserving surgery, pharmacodynamics data(end of study)