Liquid Biopsy and Pancreas Cancer: Detection of AXL(+) Functional CTCs Using EPIDROP
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- CTC-AXL measurement concordance rate
研究概览
简要总结
In solid cancers, some more aggressive tumor cells actively detach from the primary lesion and then travel through the circulating compartment to reach distant organs and form micro-metastases. These circulating tumor cells (CTCs) that have become disseminated tumor cells (DTCs) flourish in their new environments and may remain dormant for many years after the complete resection of the primary tumor. Detecting CTCs in the blood is also relevant for assessing tumor progression, prognosis and therapeutic follow-up. The non-invasive, highly sensitive for CTCs analysis is called "liquid biopsy". Pancreatic adenocarcinoma and breast cancer remain among cancers of very poor prognosis and thus represent a major therapeutic challenge. In recent years, the Axl membrane tyrosine kinase receptor has been the target of growing interest. Activation of the Gas6/Axl signaling pathway is associated with, among other things, tumor cell growth and survival, epithelial to mesenchymal transition (EMT) or drug resistances. In addition, Axl overexpression is frequently identified in patients with pancreatic adenocarcinoma and is associated with a poor prognosis. For example, the Laboratoire des Cellules Circulantes Rares Humaines (LCCRH) at the CHU and the University of Montpellier has developed two new "CTC-AXL" tests to detect CTCs expressing Axl: one using the CellSearch® (gold standard and FDA-approved) system and the other using the EPIDROP technique. The purpose of this research project is to assess the concordance of the "CTC-AXL" measurement by the innovative EPIDROP technique and the CellSearch® technique in patients with metastatic pancreatic or breast cancer.
详细描述
In solid cancers, after the formation and growth of the primary tumor, some more aggressive tumor cells actively detach from it and then travel through the circulating compartment to reach distant organs (bone marrow - liver - lung - brain…) and constitute new foci or micro-metastases. These circulating tumor cells (CTCs) that have become disseminated tumor cells (DTCs) flourish in their new environments and may remain dormant for many years after the complete resection of the primary tumor. Due to events not fully elucidated, DTCs can develop on site giving rise to macroscopic metastases but also join again the circulating compartment in the form of CTCs, swarm, colonize other organs and cause secondary metastases.
Detecting CTCs in the blood is very relevant for assessing tumor progression but also promising in terms of cancer disease prognosis and therapeutic follow-up. This new approach, published for the first time in 2010 under the term liquid biopsy, is therefore defined as a non-invasive blood test, extremely sensitive, achievable in real time and that allows the analysis of CTCs.
Currently, the choice of targeted therapies for a given patient is made after analyzing the primary tumor for expression and/or genomic status of specific molecular targets.
Many studies show that metastatic cells have phenotypic and genotypic characteristics distinct from those of most of the primary tumor. This can be explained either because metastatic cells acquire new genomic skills over time, or because a subset of metastatic sub-clone pre-exists within the primary tumor but has escaped detection by standard tissue biopsy techniques.
A direct analysis of CTCs could provide important additional information to prevent patients from inappropriate, costly treatments and harmful side effects.
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
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is at least 18 years old;
- •Patients with pancreatic cancer with remote metastases, naïve of any treatment, that is, eligible for a first line of treatment;
- •Patients with oral consent
排除标准
- •Non-affiliation or non-beneficiary of a Social Security regimen;
- •Frailty persons according to Article L1121-6 of the CSP;
- •Adult protected or unable to give consent as per Article L1121-8 of the CPMP;
- •Pregnant or lactating women as per MSC L1121-
- •Not included for monitoring difficulties (mutation, insufficient motivation, predictable poor compliance, priority associated pathology in care, etc.)
研究组 & 干预措施
Metastatic pancreatic cancer treatment-naive patients
Newly diagnosed major patients with metastatic pancreatic cancer, naïve of any treatment for metastatic disease
干预措施: Detection of circulating tumor cells expressing Axl: CTC-AXL(+) (Other)
结局指标
主要结局
CTC-AXL measurement concordance rate
时间窗: 30 days
CTC-AXL measurement concordance rate by EPIDROP (AXL(-): 0 vs AXL(+): 1) and CellSearch® (AXL(-): 0 vs AXL(+): 1)
次要结局
- Sensitivity (Se) defined as the proportion of AXL(+) positive patients (assessed by reference technique: CellSearch®) with a positive EPIDROP result(30 days)
- Specificity (Sp) defined as the proportion of AXL(-) negative patients (assessed by reference technique: CellSearch®) with a negative result by EPIDROP(30 days)
- Positive predictive value (PPV) defined as the proportion of patients with a positive EPIDROP result that is actually positive (as assessed by the reference technique: CellSearch®).(30 days)
- Number of CTC-AXL at inclusion (0 vs 1 vs 2-3 vs 4 vs 5) measured by EPIDROP(30 days)
- Number of CTC-AXL at inclusion (0 vs 1 vs 2-3 vs 4 vs 5) measured by the CellSearch technique®(30 days)
- Negative Predictive Value (VPN) defined as the proportion of patients, whose EPIDROP result is negative, that is effectively negative (assessed by reference technique: CellSearch®)(30 days)
- Overall Survival(36 months)
- Progression-Free Survival(36 months)
- Number of CTC at inclusion (0 vs 1 vs 2-3 vs 4 vs 5) measured by EPIDROP®(30 days)
- Number of CTC at inclusion (0 vs 1 vs 2-3 vs 4 vs 5) measured by the CellSearch technique®(30 days)
- CTC-PD-L1 measurement at inclusion (PD-L1(-): 0 vs PD-L1 (+): 1) measured by EPIDROP®(30 days)
- CTC-PD-L1 measurement at inclusion (PD-L1(-): 0 vs PD-L1 (+): 1) measured by the CellSearch technique®(30 days)
- Number of CTC-PD-L1 at inclusion (0 vs 1 vs 2-3 vs 4 vs 5) measured by EPIDROP®(30 days)
- Number of CTC-PD-L1 at inclusion (0 vs 1 vs 2-3 vs 4 vs 5) measured by the CellSearch technique®(30 days)
- Evaluation of circulating immune system: T cells(30 days)
- Evaluation of circulating immune system: NK cells(30 days)
- Evaluation of circulating immune system: B cells(30 days)
- Evaluation of circulating immune system: macrophages(30 days)
- Evaluation of circulating immune system: immune checkpoints(30 days)
- Evaluation of circulating immune system: platelets(30 days)