A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Objective Response rate (complete response plus partial response)
研究概览
简要总结
This study was designed to determine how effective and safe a new investigational drug, lapatinib, is in treating patients with treatment refractory or relapsed inflammatory breast cancer. Tumor tissue collected pre-treatment and at Day 28 will be examined for biologic activity by IHC (immunohistochemistry). Treatment will consist of daily oral therapy with lapatinib. A patient may continue treatment as long as they are receiving benefit. Blood samples for hematology and chemistry panels, MUGA/ECHO (multigated acquisition/echocardiogram) exams and physical exams will be performed throughout the study to monitor safety.
详细描述
This Phase II open label, multicenter study is designed to evaluate the efficacy, safety, and pharmacodynamic effects of oral lapatinib administered as a single agent therapy to patients with relapsed or refractory inflammatory breast cancer. Eligible patients must have a diagnosis of inflammatory breast cancer based on clinicopathologic criteria, tumor that is readily accessible for biopsy, and must have previously received treatment with an anthracycline and taxane-containing regimen (30 patients) plus trastuzumab (90 patients). Patients enrolled must have tumors that overexpress ErbB2, with or without co-expression of ErbB1. The primary objective for this study is to evaluate the objective response rate (defined as complete response plus partial response). Secondary objectives are to evaluate clinical benefit including quality of life parameters, progression-free survival, overall survival, time-to-response, response duration, safety and tolerability, pharmacodynamic effects on intracellular mediators that regulate tumor cell growth and survival, as well as effects on proteomic profile, and circulating levels of extracellular domains of ErbB1 and ErbB2 in peripheral blood.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 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
Lapatinib
Single arm study of lapatinib with no comparator arm.
干预措施: lapatinib (Drug)
结局指标
主要结局
Objective Response rate (complete response plus partial response)
时间窗: Week 84
次要结局
- Comparison of the effects of lapatinib on biomarkers that are involved in regulating tumor cell proliferation and survival (e.g., phosphorylated forms of Erk1/2 and Akt, STAT3, S6 Kinase, Bad, truncated ErbB2 and potentially other downstream mediators of(Day 28)
- Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR.(week 84)
- Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months(week 84)
- Calculation of progression-free survival, defined as the time between the first dose of investigational product and the first documented sign of disease progression or death.(week 84)
- Evaluation of adverse events (AEs), changes in laboratory values and echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) results from pre-dose, during dosing and post-dose assessments(week 84)
- tumor cell growth and survival) by quantitative IHC and by direct and genome-wide methods (e.g., direct sequencing and DNA microarray) in tumor tissue collected prior to and following 28 days of lapatinib monotherapy.(Day 28)
- Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment.(week 84)
- Examination of the effects of lapatinib therapy on the levels of circulating ErbB1 and ErbB2 ECD and the proteomic profile of peripheral blood. Investigation of the use of FDG-PET to predict early response to treatment with lapatinib.(Day 28)
- Clinical benefit (progression free survival, time to progression, response duration)(week 84)
- Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression.(week 84)