The Molecular Mechanism of RAS Wild-type mCRC Resistance to Anti-EGFR-antibody
2020年7月6日 更新者:Ruihua Xu、Sun Yat-sen University
The Molecular Mechanism of RAS Wild-type Metastatic Colorectal Cancer (mCRC) Resistance to Anti Epidermal Growth Factor Receptor (EGFR) Antibody
Establishing the genetic map of primary and secondary resistance of Chinese wild RAS colorectal cancer received anti-EGFR treatment through tissues and peripheral blood NGS testing.
Combination genetic data with clinical characteristics, prognosis and treatment data to explore the molecular mechanism of resistance of anti-EGFR-antibody.
研究概览
地位
完全的
条件
详细说明
Cetuximab is a chimeric (mouse/human) monoclonal antibody, an epidermal growth factor receptor (EGFR) inhibitor.
Many large clinical trials demonstrated that for RAS wild-type metastatic colorectal cancer (mCRC), especially left-sided RAS wild-type mCRC, cetuximab can prolong OS.
But some of patients have primary resistance to cetuximab and for all patients received cetuximab will develop secondary resistance.
Cell-free or circulating tumour DNA (ctDNA) including primary site and metastatic site genetic information, which can avoid tumor heterogeneity.
The results of paired test detection of tissue and ctDNA showed there is 93% consistency in RAS testing.
Therefore, dynamic monitoring ctDNA during anti-EGFR targeted treatment of RAS wild-type mCRC patients can implement prognosis of efficacy and response evaluation in real-time.
Besides, it can monitor the variation features of resistance gene and find resistance gene in real-time.
According the situation of gene change to find potential drug resistance mechanism and formulate individualization treatment plan.
研究类型
观察性的
注册 (实际的)
40
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
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Guangdong
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Guanzhou、Guangdong、中国、510060
- Medical Oncology,Sun Yat-sen University Cancer Center
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
RAS wild-type metastatic colorectal cancer patients treatment with FOLFOX/FORFIRI + cetuximab
描述
Inclusion Criteria:
- Age≥18 years, ≤75 years, all gender;
- Histologically proven metastatic adenocarcinoma of colorectal cancer, no previous history of cancer;
- The clinical data of patient is intact;
- The data of patients after surgery is intact, and the prognosis follow-up data of patient is available.
Exclusion Criteria:
- Previous history of cancer;
- Intact clinical data or diagnosis results of histopathology is unavailable;
- Time of progression disease after treatment and follow-up data are unavailable;
- Patient received blood transfusion within 3 months;
- Other situation that researchers think it will impact the results of trails or violate ethics.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
The molecular mechanism of patients primary or secondary resistance to cetuximab
大体时间:up to 36 months
|
Dynamic monitoring ctDNA to identify potential molecular mechanism of RAS wild-type mCRC patients primary or secondary resistance to cetuximab
|
up to 36 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Ying Jin, MD.,PhD、Sun Yat-sen University
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.
- Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M, Orrillo M, Abalo A, Rodriguez C, Brozos E, Vidal Y, Candamio S, Vazquez F, Ruiz J, Guix M, Visa L, Sikri V, Albanell J, Bellosillo B, Lopez R, Montagut C. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol. 2017 Jun 1;28(6):1325-1332. doi: 10.1093/annonc/mdx125.
- Stintzing S, Modest DP, Rossius L, Lerch MM, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Held S, Giessen-Jung C, Moehler M, Jagenburg A, Kirchner T, Jung A, Heinemann V; FIRE-3 investigators. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. 2016 Oct;17(10):1426-1434. doi: 10.1016/S1470-2045(16)30269-8. Epub 2016 Aug 27. Erratum In: Lancet Oncol. 2016 Oct;17 (10 ):e420. Lancet Oncol. 2016 Nov;17 (11):e479.
- Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194-201. doi: 10.1001/jamaoncol.2016.3797. Erratum In: JAMA Oncol. 2017 Dec 1;3(12):1742.
- Batth IS, Mitra A, Manier S, Ghobrial IM, Menter D, Kopetz S, Li S. Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine. Ann Oncol. 2017 Mar 1;28(3):468-477. doi: 10.1093/annonc/mdw619. Erratum In: Ann Oncol. 2019 Nov 1;30(11):1845.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年3月1日
初级完成 (实际的)
2020年3月1日
研究完成 (实际的)
2020年7月4日
研究注册日期
首次提交
2020年7月6日
首先提交符合 QC 标准的
2020年7月6日
首次发布 (实际的)
2020年7月10日
研究记录更新
最后更新发布 (实际的)
2020年7月10日
上次提交的符合 QC 标准的更新
2020年7月6日
最后验证
2020年7月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.