Innovative Approach to Detect Recurrent Colorectal Lesions With Surveillance Via Mutation Analysis & Clinical Phenotype (MTG)

Development and Clinical Utility of a New Method to Identify Patients With Risk of Recurrent Colorectal Lesions and Personalization of Their Surveillance Based on Mutation Burden and Clinical-pathological Phenotype

It is known that the development of colorectal adenoma is dependent on the appearance of somatic mutations in protooncogenes and tumor suppressor genes. Based on our previous mutation analyses of 120 patients with high-risk adenoma removed by enbloc resection with subsequent colonoscopy after 1 year, there is a correlation between mutation in exon 7 of the TP53 gene and risk of early metachronous lesions development. The results also indicate that mutation phenotype (mutation profile and burden) of all lesions detected on index colonoscopy can determine risk of metachronous lesions. As not all synchronous lesions were analyzed and the surveillance colonoscopy interval was less than 3 years, this assumption could not be confirmed. In this study it is planned to perform mutation analysis of all synchronous lesions in 200 patients and correlate the data with appearance of metachronous lesions after 1, 3 and 5 years. Moreover, the mutation profile of all metachronous lesions developed during the 5 years of surveillance will be determinated and compared with mutation profile of index lesions from the same localization to verify their common biological origin. This all could help personalize the surveillance program in terms of reduction of the burden on the patient and endoscopic workplaces and risk of developing colorectal cancer in a particular patient.

Study Overview

• Status: Recruiting
• Conditions: Predictive Cancer Model
• Intervention / Treatment: Procedure: colonoscopy

Detailed Description

The aim of this prospective study is to identify patients with recurrent colorectal lesions risk and try to design an optimal intervals of surveillance colonoscopies, especially in the high-risk group of patients, using mutation and clinical-pathologic phenotype. The partial goals are: 1. Determination of the mutation profile and mutation burden in 200 patients based on examination of all their index and synchronous lesions found during index colonoscopy using an established PCR/DCE-based heteroduplex method. 2. Clinical and histopathological evaluation and mutational profiling of all metachronous lesions found during five-year surveillance period. 3. Correlation of clinical and histopathological parameters with mutational phenotype of patient. 4. Correlation of patient's mutational phenotype with an occurrence of metachronous lesion/s during surveillance period. 5. Comparison of the mutation profile of lesions from the index period withthe mutation profile of metachronous lesions. 6. Analysis of the similarity of the mutation profile of lesions found in the same / close areas of the colorectum.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Stepan Suchanek, assoc. prof.; Phone Number: 00420 973208367; Email: stepan.suchanek@uvn.cz
• Study Contact Backup: Name: Tomas Grega, MD, Ph.D.; Phone Number: 00420 973203076; Email: tomas.grega@uvn.cz

Study Locations

• Czechia
  • Prague, Czechia, 16902
    • Recruiting
    • Military University Hospital
    • Contact: Stepan Suchanek, MD., Ph.D.; Phone Number: 00420 973208367; Email: stepan.suchanek@uvn.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with colorectal neoplasia detected in diagnostic colonoscopy.

Description

Inclusion Criteria:

• Colorectal polyp larger than 10mm removed by colonoscopy therapeutic method (EPE, EMR, ESD)
• Signed informed consent with the study and with colonoscopy

Exclusion Criteria:

• FAP, HNPCC and other hereditary CRC syndromes probands
• Colonoscopy contraindication
• Severe acute inflammatory bowel disease
• Severe comorbidities; likely non-compliance of the patient

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development and Clinical Utility of a New Method to Identify Patients With Risk of Recurrent Colorectal Lesions and Personalization of Their Surveillance Based on Mutation Burden and Clinical-pathological Phenotype	To identify patients with high risk of metachronous colorectal lesions and try to design and optimal intervals of surveillance colonoscopies, especially in the high-risk group of patients, using mutation and clinical-pathologic phenotype.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the mutation profile colorectal lesions	Determination of the mutation profile and mutation burden in 200 patients based on examination of all their index and synchronous lesions found during index colonoscopy using an established PCR/DCE-based heteroduplex method.	5 years
Mutational profil of colorectal lesions	Clinical and histopathological evaluation and mutational profiling of all metachronous lesions found during five-year surveillance period.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mutational phenotype of patient.	Correlation of clinical and histopathological parameters with mutational phenotype of patient.	5 years
Metachronous lesions	Correlation of patient's mutational phenotype with an occurrence of metachronous lesion/s during surveillance period.	5 years
Similarity of the mutation profile of lesions found in the same area	Analysis of the similarity of the mutation profile of lesions found in the same / close areas of the colorectum.	5 years

Collaborators and Investigators

• Sponsor: Military University Hospital, Prague
• Investigators: Principal Investigator: Stepan Suchanek, assoc. prof., Military University Hospital, Prague; Study Director: Ondrej Ngo, Mgr., Institute of Biostatistics and Analyses Brno; Study Director: Lucie Benesova, RNDr., Genomac Research Institute Prague; Study Chair: Ondrej Majek, RNDr., Institute of Biostatistics and Analyses Brno; Study Chair: Tereza Halkova, Mgr., Genomac Research Institute Prague

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 25, 2023
• First Submitted That Met QC Criteria: June 25, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 25, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: colonoscopy; phenotype; surveillance; colorectal neoplasia; genetic mutation; metachronous lesions
• Other Study ID Numbers: NU22-08-00424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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