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

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

Study Overview

• Status: Recruiting
• Conditions: 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 Type: Observational
• Enrollment (Anticipated): 2500

Contacts and Locations

• Study Contact: Name: Dmitrii Semenov, PhD; Phone Number: +7 (985) 2632870; Email: dr.semenov@inbox.ru
• Study Contact Backup: Name: Alexey Tsukanov, PhD; Phone Number: +7 (916) 7563957; Email: tsukanov81@rambler.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 123423
    • Recruiting
    • State Scientific Centre of Coloproctology
    • Contact: Alexey Tsukanov, Phd; Phone Number: +79167563957; Email: tsukanov81@rambler.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of occurrence of microsatellite instability/deficiency	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.	up to 5 years
Spectrum of germinal mutations in Lynch syndrome	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.	up to 5 years
Spectrum of malignant neoplasms	The family history of all oncological diseases will be studied to find out the main target organs of patients with Lynch syndrome in Russia	up to 5 years
Effectiveness of therapy with immune checkpoint inhibitors	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	up to 5 years
Impact of the presence of microsatellite instability/deficiency	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	up to 5 years

Collaborators and Investigators

• Sponsor: State Scientific Centre of Coloproctology, Russian Federation
• Collaborators: The Loginov MCSC MHD; Pirogov National Medical and Surgical Center; Moscow City Oncological Hospital No. 62 MHD; City Clinical Oncological Hospital No. 1 MHD; MMCC Kommunarka MHD; D.D. Pletnev City Clinical Hospital MHD; Botkin Hospital MHD; Clinic K+31
• Investigators: Principal Investigator: Alexey Tsukanov, PhD, Head of the Department of Laboratory Genetics

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): December 31, 2028

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Frequency; Lynch Syndrome; MSI; Hereditary Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms; Neoplasms by Site; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Syndrome; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis
• Other Study ID Numbers: 01082022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Before the start of the study, at the initiating visit, the monitor, together with the researchers and their staff, will review the protocol and the CRF. During the study, the monitor will regularly communicate remotely with the research center and check the process of inclusion of patients, the completeness of maintaining medical records of patients, the correctness of filling out the CRF. The researcher must provide the monitor with access to the relevant hospital documentation and other medical records to verify their compliance with the data recorded in the IRC. The data identifying the patient's identity will remain confidential.
• IPD Sharing Time Frame: 6 months after completion of the study
• IPD Sharing Access Criteria: upon the request
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No