A Phase Ib/II Study Investigating the Combination of Everolimus With Trastuzumab and Paclitaxel in Patients With HER2-overexpressing Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 12
- 主要终点
- Phase II: Overall Response Rate
研究概览
简要总结
Phase I: will look at different dose levels and regimens of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
Phase II: will assess the efficacy and safety of the 10mg daily dose of everolimus combined with weekly trastuzumab and paclitaxel therapy in patients with HER-2 overexpressing metastatic breast cancer.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female or male patients ≥ 18 years old with WHO performance status ≤ 1
- •HER-2 over-expressing metastatic breast cancer cells confirmed by histology
- •Progressive disease on prior trastuzumab alone/or in combination with other anticancer agents, or relapsed any time after completion of this therapy (phase l)
- •Patient resistance to trastuzumab and taxanes (Phase ll)
- •Measurable disease according to RECIST (Phase ll)
- •Patients neurologically stable with adequate bone marrow, liver and renal function
排除标准
- •Patients receiving endocrine therapy for breast cancer ≤ 2 weeks prior to study treatment start
- •Patients currently receiving chemotherapy, immunotherapy or radiotherapy or who have received these ≤ 4 weeks prior to study treatment start or patients who have received lapatinib ≤ 2 weeks prior to study treatment start
- •Patients who have previously received mTOR inhibitors
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Phase I - RAD001 5mg + PT, daily
Daily dosing schedule of EPT = Paclitaxel & Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.
干预措施: Everolimus (Drug)
Phase I - RAD001 5mg + PT, daily
Daily dosing schedule of EPT = Paclitaxel & Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.
干预措施: Trastuzumab (Drug)
Phase I - RAD001 5mg + PT, daily
Daily dosing schedule of EPT = Paclitaxel & Trastuzumab verolimus 5mg plus Paclitaxel plus Trastuzumab.
干预措施: Paclitaxel (Drug)
Phase I - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
干预措施: Everolimus (Drug)
Phase I - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
干预措施: Trastuzumab (Drug)
Phase I - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
干预措施: Paclitaxel (Drug)
Phase I - RAD001 30mg + PT, weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
干预措施: Everolimus (Drug)
Phase I - RAD001 30mg + PT, weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
干预措施: Trastuzumab (Drug)
Phase I - RAD001 30mg + PT, weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
干预措施: Paclitaxel (Drug)
Phase II - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
干预措施: Everolimus (Drug)
Phase II - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
干预措施: Trastuzumab (Drug)
Phase II - RAD001 10mg + PT, daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Phase II: Overall Response Rate
时间窗: every 8 - 9 weeks until disease progression or a new lesion is identified
The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
次要结局
- Phase I: Best Overall Response (BOR)(every 8 - 9 weeks until disease progression or a new lesion is identified)
- Phase II: Progression Free Survival (PFS)(every 8 - 9 weeks until disease progression or a new lesion is identified)
- Phase II: Overall Survival (OS)(every 3 months until death)