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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Completed

CT.gov ID

NCT04482608

Collaborator

The Second Affiliated Hospital of Kunming Medical University (Other)

671

Enrollment

Location

9.2

Actual Duration (Months)

72.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Mismatch Repair Deficiency Microsatellite Instability High

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 Design

Study Type:

Observational

Actual Enrollment :

671 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

The Metastatic Colorectal Cancer Patients With Proficient Mismatch Repair (pMMR) / Microsatellite Stable (MSS) or Deficient Mismatch Repair (dMMR) / Microsatellite Instability High (MSI-H) Status Received Palliative Chemotherapy Efficacy and Survival

Actual Study Start Date :

Sep 1, 2019

Actual Primary Completion Date :

Apr 1, 2020

Actual Study Completion Date :

Jun 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
pMMR/MSS mCRC patients The metastatic colorectal cancer patients with proficient mismatch repair or microsatellite stable status.
dMMR/MSI-H mCRC patients The metastatic colorectal cancer patients with deficient mismatch repair or microsatellite instability high status.

Outcome Measures

Primary Outcome Measures

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

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)
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)
Overall survival [up to approximately 9 year]
The time from registration to death due to any cause, or censored at date last known alive.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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