A Phase II, Randomized, Multi-center Study, Assessing Value of Adding Everolimus (RAD001) to Trastuzumab as Preoperative Therapy of HER-2 Positive Primary Breast Cancer Amenable to Surgery.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- UNICANCER
- 入组人数
- 82
- 试验地点
- 8
- 主要终点
- Efficacy as measured by clinical and echographic tumor evaluation
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with trastuzumab is more effective than giving trastuzumab alone in treating women with breast cancer.
PURPOSE: This randomized phase II trial is studying trastuzumab and everolimus to see how well they work compared to trastuzumab alone before surgery in treating patients with breast cancer that can be removed by surgery.
详细描述
OBJECTIVES:
Primary
- To evaluate the added efficacy obtained by the association of trastuzumab (Herceptin®) with everolimus as preoperative therapy of primary HER2-positive breast cancer as shown by increased clinical tumor response rate.
Secondary
- To compare the inhibition of the two pathways, RAS/RAF/MAP kinase and PI3-kinase/AKT/mTor.
- To evaluate whether the pre-treatment molecular characteristics of tumor and serum or their modifications early in the treatment are predictive of clinical response.
- To compare the frequency of pathological complete response achieved in the two groups after 6 weeks of treatment.
- To determine disease-free survival at 3 years.
- To evaluate safety and tolerability of the two treatment regimens.
- To analyze the possible relationships between treatment toxicity and constitutional gene polymorphisms linked to the administered agents.
- To analyze the possible relationships between response and molecular pharmacodynamic assessments, including proteomics (blood samples), Bio-Plex protein array (tumor), and IHC (tumor).
- To analyze the drug levels and pharmacokinetic assessments of everolimus and trastuzumab (Herceptin®).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients then undergo surgery.
干预措施: trastuzumab (Biological)
Arm I
Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients then undergo surgery.
干预措施: therapeutic conventional surgery (Procedure)
Arm II
Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery.
干预措施: trastuzumab (Biological)
Arm II
Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery.
干预措施: everolimus (Drug)
Arm II
Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery.
干预措施: therapeutic conventional surgery (Procedure)
结局指标
主要结局
Efficacy as measured by clinical and echographic tumor evaluation
时间窗: january 2013
次要结局
- Disease-free survival at 3 years(January 2015)
- Pathological response assessed after 6 weeks of treatment(January 2013)
- Clinical response predictive factors(May 2013)
- Rate of pathological complete response (pCR)(January 2013)
- Pharmacogenomics, proteomics, immunohistochemistry (IHC), pharmacokinetics(december 2013)
- Toxicity as assessed by the standard NCI CTC-AE v3.0 scale(January 2013)