The mCRC Patients With pMMR/MSS or dMMR/MSI-H Status Received Palliative Chemotherapy Efficacy and Survival

Completed

• Conditions: Mismatch Repair Deficiency; Colorectal Cancer Metastatic; Microsatellite Instability High

• Registration Number: NCT04482608
• Lead Sponsor: Sun Yat-sen University

Brief Summary

Deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) accounts for 4-5% in metastatic colorectal cancer (mCRC). The efficacy and survival of patients with dMMR/MSI-H status received palliative chemotherapy have not clear yet. In this study, the investigators observed the efficacy and survival of dMMR/MSI-H status mCRC patients received palliative first-line chemotherapy.

Detailed Description

Colorectal cancer (CRC) is the one of most common cancer in the world. Loss of function of DNA mismatch repair (MMR) is an important mechanism of CRC development. Mutation or modification of MMR genes result in MMR protein deficient (dMMR) and microsatellite instability (MSI). It has been reported that the dMMR or MSI high (MSI-H) phenotype is present in approximately 15-18% of CRC patients. Most dMMR/MSI-H tumors are sporadic CRC, and only approximately 3% of dMMR/MSI-H tumors are Lynch syndrome (LS) or hereditary nonpolyposis colorectal carcinoma (HNPCC).

The dMMR/MSI-H status was reported to be a predictive marker for adjuvant chemotherapy. Multiple retrospective studies showed that dMMR/MSI-H is correlated with a favorable prognosis in stage II/III CRC. Previous studies suggested that dMMR/MSI status may be a predictive marker of decreased benefit form adjuvant monotherapy of 5-fluorouracil (5-FU) in patients with stage II disease, but not in those with stage III disease. For metastatic colorectal cancer (mCRC), the relationship of the MMR/MSI phenotype and prognosis is unclear. Some researchers found that CRC patients with the dMMR/MSI-H phenotype have a worse prognosis. But other researchers thought the dMMR/MSI-H phenotype is no associate to efficacy and survival of palliative chemotherapy, even is benefit for efficacy and survival.Therefore, the aim of this study was to clarify whether the status of dMMR/MSI-H affected progression-free survival (PFS) in mCRC patients who received first-line palliative chemotherapy.

Study Timeline

• Study Start: 2019-09-01
• Primary Completion: 2020-04-01
• Study Completion: 2020-06-08
• Status Verified: 2020-07
• Study First Submitted: 2020-07-18
• Study First Submitted QC: 2020-07-18
• Study First Posted: 2020-07-22
• Last Update Submitted: 2020-07-23
• Last Update Posted: 2020-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 671

Inclusion Criteria

1. Age ≥ 18 years old
2. Histologically confirmed Metastatic colorectal adenocarcinoma;
3. Immunohistochemistry confirmed mismatch repair status or polymerase chain reaction (pCR) / next-generation sequencing (NGS) confirmed microsatellite status
4. Received palliative chemotherapy and have complete information of treatment

Exclusion Criteria

1. Patients have not tested for mismatch repair or microsatellite
2. Patients have not received palliative chemotherapy or received palliative chemotherapy but treatment information incomplete

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	up to 24-36 months	PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to approximately 9 year	The time from registration to death due to any cause, or censored at date last known alive.
Disease Control Rate (DCR)	From first patient first visit to 6 month after last patient first visit	Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Response rate	From first patient first visit to 6 month after last patient first visit	Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Trial Locations

Locations (1)

Sun yat-sen university cancer center; 🇨🇳 Guangzhou, Guangdong, China