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

Predictive Cancer Model Clinical Trial

— MTG  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05929365
• Other study ID #: NU22-08-00424
• Status: Recruiting
• Start date: May 1, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2023
• Source: Military University Hospital, Prague
• Contact: Stepan Suchanek, assoc. prof.
• Phone: 973208367
• Email: stepan.suchanek[@]uvn.cz
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Predictive Cancer Model

Intervention

Procedure:
• colonoscopy
determine the mutation profile of resected colorectal neoplasia

Locations

Country	Name	City	State
Czechia	Military University Hospital	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Military University Hospital, Prague

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mutational phenotype of patient.	Correlation of clinical and histopathological parameters with mutational phenotype of patient.	5 years
Other	Metachronous lesions	Correlation of patient's mutational phenotype with an occurrence of metachronous lesion/s during surveillance period.	5 years
Other	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
Primary	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	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
Secondary	Mutational profil of colorectal lesions	Clinical and histopathological evaluation and mutational profiling of all metachronous lesions found during five-year surveillance period.	5 years