MSIRus22: Prospective Multicenter Registry Study to Assess the Frequency of Lynch Syndrome Among Patients With Colorectal Cancer

Sponsor

State Scientific Centre of Coloproctology, Russian Federation (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05495776

Collaborator

The Loginov MCSC MHD (Other), Pirogov National Medical and Surgical Center (Other), Moscow City Oncological Hospital No. 62 MHD (Other), City Clinical Oncological Hospital No. 1 MHD (Other), MMCC Kommunarka MHD (Other), D.D. Pletnev City Clinical Hospital MHD (Other), Botkin Hospital MHD (Other), Clinic K+31 (Other)

2,500

Enrollment

Location

Anticipated Duration (Months)

32.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Lynch Syndrome Hereditary Colorectal Cancer MSI

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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

2500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Patients with colorectal cancer Patients with colon adenocarcinoma who have not previously received antitumor treatment (chemo/radiation therapy) for a currently detected tumor

Outcome Measures

Primary Outcome Measures

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

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.
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;