The Molecular Mechanism of RAS Wild-type mCRC Resistance to Anti-EGFR-antibody

Completed

• Conditions: Colorectal Cancer

• Registration Number: NCT04466267
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2017-03-01
• Primary Completion: 2020-03-01
• Status Verified: 2020-07
• Study Completion: 2020-07-04
• Study First Submitted: 2020-07-06
• Study First Submitted QC: 2020-07-06
• Last Update Submitted: 2020-07-06
• Study First Posted: 2020-07-10
• Last Update Posted: 2020-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Age≥18 years, ≤75 years, all gender;
2. Histologically proven metastatic adenocarcinoma of colorectal cancer, no previous history of cancer;
3. The clinical data of patient is intact;
4. The data of patients after surgery is intact, and the prognosis follow-up data of patient is available.

Exclusion Criteria

1. Previous history of cancer；
2. Intact clinical data or diagnosis results of histopathology is unavailable;
3. Time of progression disease after treatment and follow-up data are unavailable;
4. Patient received blood transfusion within 3 months;
5. Other situation that researchers think it will impact the results of trails or violate ethics.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The molecular mechanism of patients primary or secondary resistance to cetuximab	up to 36 months	Dynamic monitoring ctDNA to identify potential molecular mechanism of RAS wild-type mCRC patients primary or secondary resistance to cetuximab

Trial Locations

Locations (1)

Medical Oncology,Sun Yat-sen University Cancer Center; 🇨🇳 Guanzhou, Guangdong, China