A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- To estimate the clinical benefit rate of the combination of ZD 1839 and docetaxel; clinical benefit measured by clinical response, pathologic response, and stable disease (SD greater than or equal to 24 weeks)
研究概览
简要总结
The purpose of this study is to learn how breast cancer tumors respond to treatment combining the drugs docetaxel and ZD1839.
详细描述
Patients with advanced breast cancer continue to have an extremely poor prognosis with an average life expectancy of approximately 2 years. Novel treatments designed to exploit biologic properties of the tumor are urgently required as a means to improve the outcome for the large numbers of patients who relapse after receiving optimal chemotherapy treatments.
Overexpresssion of EGFR and/or TGF-alpha is frequent in human breast cancer and has been correlated in many cases with poor prognostic features. Inhibition of the EGFR pathway has been proposed as a potential therapeutic modality in advanced breast cancer. The antiproliferative activity of ZD 1839 in combination with cytotoxic drugs, such as docetaxel was evaluated in breast cancer cell lines ZR-75-1 and MCF-10A ras that coexpress EGFR and TGF-alpha. Combination treatment demonstrated dose dependent supra-additive growth inhibition and markedly enhanced apoptotic cell death.
Although taxanes bind to the microtubular network in cells that is essential for mitotic and interphase cellular functions, the mechanism by which these agents induce cell death is not entirely clear. Docetaxel has also shown dose-dependent anti-angiogenic activity. Thus, the mechanism(s) of anti-tumor activity of docetaxel remain unclear and combinations of signal transduction pathway inhibition and/or anti-angiogenesis may provide potentiation of concurrent ZD 1839 and docetaxel therapy.
This phase 2 trial is designed to prospectively investigate the efficacy and safetey of combination therapy with ZD 1839 and docetaxel in patients with 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 —（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
结局指标
主要结局
To estimate the clinical benefit rate of the combination of ZD 1839 and docetaxel; clinical benefit measured by clinical response, pathologic response, and stable disease (SD greater than or equal to 24 weeks)
时间窗: 2 years
To characterize the safety profile of the combination of ZD 1839 and docetaxel as measured by the frequency and severity of adverse events.
时间窗: 2 years
次要结局
- To estimate the duration of clinical benefit.(2 years)
- To estimate the objective tumor response rate (using RECIST best overall response of CR + PR).(2 years)
- To estimate the duration of tumor response.(2 years)
- To estimate progression-free survival.(2 years)
- To estimate time to treatment failure by measuring time to treatment failure (includes disease progression, second primary cancer, death from any cause, or discontinuation of protocol therapy in the absence of disease progression).(2 years)