Liquid Biopsy: Intercepting Mutational Trajectories of HER2 Breast Cancer Inpatients Under T-DM1 Treatment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 9
- 主要终点
- Number of de novo mutations
研究概览
简要总结
This is an open, interventional, non-pharmacological, prospective study. Patients will receive trastuzumab emtansine (T-DM1) at 3.6 mg/kg intravenously every 21 days, as per Summary of Product Characteristics (SmPC). This is a no-profit study.
详细描述
T-DM1 effects will be monitored by a combination of Next Generation Sequencing (NGS, tumor tissue) and Liquid Biopsy (LB, blood), as described below, to capture molecular events (gene aberrations, mainly mutations) associated with (or causative of) relapse as well as primary/adaptive resistance to HER2 blockade.
This study will prospectively monitor these events throughout the clinical history of the patients (archival tissues, blood collection, aimed biopsies). No investigational drugs will be administered.
This protocol is classified as "interventional" for two reasons:
- dedicated, additional blood drawings (liquid biopsies)are collected in addition to the routine bloodtests being requested as per standard clinical practice;
- the study involves occasional fine-needle biopsy on accessible (e.g. cutaneous) metastatic foci in selected patients to confirm their HER2 status, as per good medical practice.
These will represent an additional opportunity of targeted NGS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
结局指标
主要结局
Number of de novo mutations
时间窗: About 4 years
3. Number of de novo mutations arising during T-DM1 treatment. Few mutations and gene aberrations (see above) are known to associate with primary and acquired resistance to Trastuzumab (TTZ) and Pertuzumab (PTZ), and none is specifically associated with T-DM1 escape, to our knowledge. Possibly, this is due to the rather recent introduction of this antibody-drug conjugate in human therapy.
Rate of response/anticipation of relapse
时间窗: About 4 years
2. Changes form baseline in thr response rate. First detection of index mutations in blood will be compared with first imaging and medical evidence of relapse (response rate) to determine whether and how the LiqERBcept protocol can lead to earlier detection and improvement in medical care.
Number of index mutations
时间窗: About 4 years
1. Number of index mutations and resistance-associated mutations in the bloodstream. Index mutations are defined as the number of mutation detected in tissue biopsies from either or both the primary lesions and the most recent recurrence, whenever available. Resistance mutations known to arise during non-T-DM1 HER2-blockade include mutations of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1), AKT1 (AKT1 AKT serine/threonine kinase 1), and EGF1R (Epidermal Growth Factor Receptor 1).These may be a special case of index mutations. Other known genomic aberrations occurring under HER2 blockade and potentially testable in bloodier PTEN (Phosphatase and tensin homolog) loss and overexpression of p95HER2 (p95HER2/611 carboxy terminal fragment), MUC4 (Mucin 4, Cell Surface Associated), and PDK1 (3-Phosphoinositide-dependent kinase 1)
次要结局
- Number of actionable mutations(About 4 years)