Clinical trial NCT04482608: The mCRC Patients With pMMR/MSS or dMMR/MSI-H Status Received Palliative Chemotherapy Efficacy and Survival
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer Metastatic
Mismatch Repair Deficiency
Microsatellite Instability High
Keywords: Colorectal Cancer Metastatic
Mismatch Repair Deficiency
Microsatellite Instability High
Chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: The Second Affiliated Hospital of Kunming Medical University
First posted: 2020-07-22
Enrollment: 671
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The metastatic colorectal patients with different MMR or microsatellite status received palliative chemotherapy

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: up to 24-36 months
Secondary outcomes:
measure: Response rate
timeFrame: From first patient first visit to 6 month after last patient first visit
measure: Disease Control Rate (DCR)
timeFrame: From first patient first visit to 6 month after last patient first visit
measure: Overall survival
timeFrame: up to approximately 9 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun yat-sen university cancer center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ying Jin, MD.,PhD
role: PRINCIPAL_INVESTIGATOR
References: