Effect of Perioperative AntiHER-2 Therapy on Early Breast Cancer Study - Biological Phase (EPHOS-B)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 257
- 试验地点
- 1
- 主要终点
- Increase in apoptosis, by change in the tumor (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery (biological phase)
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. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trastuzumab or lapatinib ditosylate is more effective in treating women with early breast cancer.
Update June 2013:
Since the initial development of EPHOS-B in 2007 more evidence in relation to safety and efficacy of anti-HER2 therapies are now available, and in particular, a growing body of evidence that combinations of two anti-HER2 therapies are more effective than monotherapies. Therefore this study has been amended (PART 2) to a 1:1:2 ratio to control, perioperative trastuzumab or the combination of lapatinib and trastuzumab.
PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works compared with lapatinib ditosylate (and in since June 2013 - compared with a combination of lapatinib and trastuzumab) in treating women with early breast cancer.
详细描述
OBJECTIVES:
Primary
- To determine whether pre-operative treatment of HER-2 positive breast cancer patients with anti-HER2 therapy consisting of trastuzumab (Herceptin®) vs lapatinib ditosylate inhibits proliferation or increases apoptosis.
- To compare the effects of trastuzumab (Herceptin®), lapatinib ditosylate and the combination of lapatinib ditosylate and trastuzumab (Herceptin®) on the inhibition of proliferation or increase of apoptosis
Secondary
- To determine whether pre-operative anti-HER2 treatment reduces serum angiogenic factors.
- To identify molecular predictors of biological response to anti-HER2 therapy
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
Part 1: Control
No peri-operative therapy given
干预措施: laboratory biomarker analysis (Other)
Part 1: Control
No peri-operative therapy given
干预措施: therapeutic conventional surgery (Procedure)
Part 1: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: trastuzumab (Biological)
Part 1: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: laboratory biomarker analysis (Other)
Part 1: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: adjuvant therapy (Procedure)
Part 1: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: neoadjuvant therapy (Procedure)
Part 1: lapatinib
Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery
干预措施: lapatinib ditosylate (Drug)
Part 1: lapatinib
Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery
干预措施: laboratory biomarker analysis (Other)
Part 1: lapatinib
Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery
干预措施: adjuvant therapy (Procedure)
Part 1: lapatinib
Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery
干预措施: neoadjuvant therapy (Procedure)
Part 2: Control
No peri-operative therapy
干预措施: laboratory biomarker analysis (Other)
Part 2: Control
No peri-operative therapy
干预措施: therapeutic conventional surgery (Procedure)
Part 2: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: trastuzumab (Biological)
Part 2: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: laboratory biomarker analysis (Other)
Part 2: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: adjuvant therapy (Procedure)
Part 2: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
干预措施: neoadjuvant therapy (Procedure)
Part 2: lapatinib-trastuzumab combination
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.
干预措施: trastuzumab (Biological)
Part 2: lapatinib-trastuzumab combination
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.
干预措施: lapatinib ditosylate (Drug)
Part 2: lapatinib-trastuzumab combination
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.
干预措施: laboratory biomarker analysis (Other)
Part 2: lapatinib-trastuzumab combination
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.
干预措施: adjuvant therapy (Procedure)
Part 2: lapatinib-trastuzumab combination
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.
干预措施: neoadjuvant therapy (Procedure)
结局指标
主要结局
Increase in apoptosis, by change in the tumor (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery (biological phase)
时间窗: 10-13 days
Fall in proliferation between diagnosis and surgery by change in proliferation measured by Ki67 immunohistochemical assessment (%) at diagnosis and at surgery (biological phase)
时间窗: 10-13 days
Relapse-free survival (clinical phase)
时间窗: TBC
次要结局
- Changes in the angiogenic serum markers VEGF-A, VEGF R1, and CD105, measured at diagnosis, surgery (plus also tumor CD31) and 28-30 days post surgery (biological phase)(TBC)
- Time to distant recurrence (clinical phase)(TBC)
- Pre-treatment and/or surgical expression of molecular markers (EGFR, Her-3, IGF1R, c-myc, AKT, p-ERK, pS6 inase, activated src, or truncated p95HER-2 expression)(TBC)
- Overall survival (clinical phase)(TBC)
- Time to local recurrence (clinical phase)(TBC)