A Phase II Study Evaluating The Efficacy And Tolerability Of Everolimus (RAD001) In Combination With Trastuzumab And Vinorelbine In The Treatment Of Progressive HER2-Positive Breast Cancer Brain Metastases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 4
- 主要终点
- Intracranial Objective Response Rate- Modified RECIST Criteria
研究概览
简要总结
Purpose: This study is a single-arm, open-label phase II clinical trial testing the hypothesis that daily everolimus plus weekly vinorelbine and trastuzumab will be effective, safe, and tolerable among patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases. Once enrolled, patients will receive everolimus PO daily in combination with weekly intravenous (IV) vinorelbine and trastuzumab. Cycles will be repeated every 3 weeks (21 days). At the time of progression, patients will come off study.
Participants: Up to 35 adults over 21 with HER-2 positive breast cancer that has metastasized to the brain.
详细描述
STUDY OBJECTIVES Primary Objective -To determine the intracranial objective response rate of mTOR inhibition (everolimus) in combination with vinorelbine and trastuzumab in the treatment of HER2-positive, progressive breast cancer brain metastases as defined via modified RECIST criteria.
Secondary Objectives
- To determine the intracranial objective response rate of mechanistic target of rapamycin (mTOR) inhibition (everolimus) in combination with vinorelbine and trastuzumab in the treatment of HER2-positive, progressive breast cancer brain metastases as defined by MacDonald criteria.
- To evaluate the safety and tolerability of everolimus in combination with trastuzumab and vinorelbine as assessed via the NCI CTCAE version 4.0
- To evaluate time to intracranial progression after administration of everolimus in combination with trastuzumab and vinorelbine as defined via modified RECIST criteria
- To evaluate the extracranial objective response rate as determined by RECIST 1.1 criteria after administration of everolimus in combination with trastuzumab and vinorelbine.
- To evaluate the extracranial time to progression as determined by RECIST 1.1 criteria after administration of everolimus in combination with trastuzumab and vinorelbine.
- To evaluate progression free survival (PFS) and overall survival (OS) after administration of everolimus in combination with trastuzumab and vinorelbine.
- To evaluate the impact of everolimus in combination with trastuzumab and vinorelbine on quality of life as measured by the Functional Assessment of Cancer Therapy Breast (FACT-B) and Functional Assessment of Cancer Therapy Brain (FACT-Br) questionnaires.
Exploratory Objective
-To evaluate biomarkers in archival tumor tissue samples and correlate with therapeutic response to everolimus in combination with vinorelbine and trastuzumab.
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
- 21 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
Everolimus +Vinorelbine + trastuzumab
daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab
干预措施: Everolimus (Drug)
Everolimus +Vinorelbine + trastuzumab
daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab
干预措施: Vinorelbine (Drug)
Everolimus +Vinorelbine + trastuzumab
daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Intracranial Objective Response Rate- Modified RECIST Criteria
时间窗: 3 years
response will be evaluated via gadolinium-enhanced brain MRI using modified RECIST criteria. Complete Response (CR) - Disappearance of all target and nontarget lesions Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion. Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started. Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.
次要结局
- Intracranial Response Rate- MacDonald Criteria(3 years)
- Toxicity(24 weeks)
- Time to Intracranial Progression.(3 years)
- Extracranial Response(3 years)
- Extracranial Time to Progression(3 years)
- Overall Survival(3 years)
- Functional Assessment of Cancer Therapy- Brain (FACT-Br) Change From Baseline to Assess Impact of Everolimus in Combination With Trastuzumab and Vinorelbine on Quality of Life(9 weeks)
- Functional Assessment Cancer Therapy- Breast (FACT-B) From Baseline to 9 Weeks of Treatment to Assess Impact of Everolimus in Combination With Trastuzumab and Vinorelbine on Quality of Life(9 weeks)