Phase 1 Study of the Combination of Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide
研究概览
简要总结
Objectives:
Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomideSecondary - Obtain preliminary information on the clinical anti-tumor activity of lapatinib plus temozolomide on brain metastases secondary to HER-2 positive breast cancer including Objective Response Rate (ORR), Clinical Benefit (CB) and Duration of Response (DR)
Methodology:
Phase I, single-centre, open-label, dose-escalation study of combining lapatinib and temozolomide in HER-2 positive breast cancer patients with progressive brain metastases after surgery or radiotherapy or radiosurgery
Treatment:
Temozolomide will be given orally for 5 days of every 28 days, at doses of either 100mg/m2/day or 150mg/m2/day or 200mg/m2/day AND Lapatinib will be given orally every day at either 1000mg/day or 1250mg/day or 1500mg/day.Sequential cohorts will be escalated in increments according to the dose escalation scheme, and determined by dose limiting toxicities.
详细描述
Patients selection criteria:
- age 18 - 70 years
- Women with cytologically or histologically proven metastatic breast cancer with recurrent / progressive brain metastases evaluable by MRI, after standard treatment with surgery (at least 3 weeks prior) or WBRT (at least 3 weeks prior) or stereotactic RT (at least 1 week prior); or otherwise deemed as unsuitable for standard treatment in the first instance
- Known HER-2 positive status (immunohistochemistry (IHC) 3+ Fluorescence In Situ Hybridization (FISH) positive )
- Previous chemotherapy (adjuvant and metastatic regimens) allowed
- Previous treatment with trastuzumab allowed (Trastuzumab to be discontinued prior to study entry)
- At least one measurable lesion in the brain, defined as any lesion >5mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
- Expected life-expectancy of more than 3 months
- ECOG performance status of 0, 1 or 2
- Adequate bone marrow, renal and hepatic functionsLVEF
- LVEF 50% measured by echocardiography or MUGA scan
- Concomitant corticosteroids and anti-convulsants for symptomatic brain metastases are allowed
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •18 - 70 years
- •Women with cytologically or histologically proven metastatic breast cancer with recurrent / progressive brain metastases evaluable by MRI, after standard treatment with surgery (at least 3 weeks prior) or WBRT (at least 3 weeks prior) or stereotactic RT (at least 1 week prior); or otherwise deemed as unsuitable for standard treatment in the first instance
- •Known HER-2 positive status (immunohistochemistry (IHC) 3+ Fluorescence In Situ Hybridization (FISH) positive )
- •Previous chemotherapy (adjuvant and metastatic regimens) allowed
- •Previous treatment with trastuzumab allowed (Trastuzumab to be discontinued prior to study entry)
- •At least one measurable lesion in the brain, defined as any lesion >5mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
- •Expected life-expectancy of more than 3 months
- •ECOG performance status of 0, 1 or 2
- •Adequate bone marrow, renal and hepatic functionsLVEF
- •LVEF >50% measured by echocardiography or MUGA scan
- •Concomitant corticosteroids and anti-convulsants for symptomatic brain metastases are allowed
排除标准
- 未提供
研究组 & 干预措施
I
Lapatinib plus temozolomide
干预措施: lapatinib and temozolomide (Drug)
结局指标
主要结局
Primary - Determine the maximum tolerated dose (MTD) and evaluate the dose limiting toxicities (DLT) of combining lapatinib and temozolomide
时间窗: 18 months
次要结局
- Obtain preliminary information on the clinical anti-tumor activity of lapatinib plus temozolomide on brain metastases secondary to HER-2 positive breast cancer including Objective Response Rate, Clinical Benefit and Duration of Response(18 months)