Prospective Multicenter Registry Study to Assess the Frequency of Lynch Syndrome Among Patients With Colorectal Cancer

Recruiting

• Conditions: Lynch Syndrome; MSI; Colorectal Cancer; Hereditary Colorectal Cancer

• Registration Number: NCT05495776
• Lead Sponsor: State Scientific Centre of Coloproctology, Russian Federation

Brief Summary

Prospective multicenter registry study to assess the frequency of Lynch syndrome among patients with colorectal cancer in Russia

Detailed Description

Blood and tumor samples will be obtained from enrolled patients. 4 ml of venous blood samples will be taken into a tube with EDTA and stored at -20 0C. Tumor samples will be taken during endoscopy or surgical treatment, embedded in paraffin and stored at room temperature.

Microsatellite instability in the tumor tissue will be determined by any method available in the participating center (immunohistochemical or molecular genetic study). In case of detection of microsatellite instability/deficiency in the repair system of unpaired bases blood samples will be analyzed for the fact that germinal mutations in the DNA mismatch repair genes.

Patients will be followed up for 5 years after enrollment. During follow up correlation of spectrum of germinal mutations with clinical data, effectiveness of therapy with immune checkpoint inhibitors, the spectrum of malignant neoplasms in the families of patients with Lynch syndrome, the impact of the presence of microsatellite instability/deficiency in the DNA mismatch repair genes on treatment tactics in the Russian Federation will be assessed.

Study Timeline

• Study First Submitted: 2022-07-29
• Status Verified: 2022-08
• Study Start: 2022-08-01
• Study First Submitted QC: 2022-08-08
• Study First Posted: 2022-08-10
• Last Update Submitted: 2022-10-24
• Last Update Posted: 2022-10-25
• Primary Completion: 2025-08-01
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2500

Inclusion Criteria

• Provision of written informed consent;
• Patients with histologically verified colon adenocarcinoma or patients with histologically verified synchronous neoplasms who have not previously received treatment for a second tumor;
• Age ≥ 18 years;
• Absence of antitumor treatment for a real tumor (it is allowed to include patients who have a history of antitumor treatment for other malignant tumors, if the period after treatment is more than 12 months).
• The ability of the patient, according to the Researcher, to fulfill the requirements of the Protocol;

Exclusion Criteria

• Patients receiving chemotherapy or radiotherapy for colon cancer at the time of screening

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Frequency of microsatellite instability and Lynch syndrome	up to 5 years	To assess the frequency of microsatellite instability and Lynch syndrome in the population of patients with colorectal cancer in the Russian Federation.

Secondary Outcome Measures

Name	Time	Method
Effectiveness of therapy with immune checkpoint inhibitors	up to 5 years	The frequency will be compared: the frequency of objective response rate (RECIST 1.1) while using immune checkpoint inhibitors in metastatic colon cancer and microsatellite instability associated/not associated with Lynch syndrome
Spectrum of malignant neoplasms	up to 5 years	The family history of all oncological diseases will be studied to find out the main target organs of patients with Lynch syndrome in Russia
Frequency of occurrence of microsatellite instability/deficiency	up to 5 years	Assessment of the frequency of occurrence of microsatellite instability/deficiency in the repair system of unpaired bases in second tumors in patients with colorectal cancer of various stages.
Spectrum of germinal mutations in Lynch syndrome	up to 5 years	The mlh1, msh2, msh6, pms2 and epcam genes will be examined for the presence of all types of pathogenic variants in patients with MSI in colon tumor. The possible correlation of gene-phenotype and pathogenic variants of each gene-phenotype will also be studied. To detect MSI in a tumor sample, need to do the fragment analysis (markers NR21, NR24, NR27, BAT25, BAT26). Рatients with MSI in the tumor will have DNA diagnostics of MMR EPCAM genes by sequencing and MLPA . The MMR and EPCAM genes will be examined in DNA isolated from blood lymphocytes.
Impact of the presence of microsatellite instability/deficiency	up to 5 years	The frequency of adjuvant chemotherapy in stages II-III of colon cancer in the presence of microsatellite instability / deficiency in the repair system of unpaired bases in real clinical practice will be evaluated

Trial Locations

Locations (1)

State Scientific Centre of Coloproctology; 🇷🇺 Moscow, Russian Federation