Clinical trial NCT05929365: Innovative Approach to Detect Recurrent Colorectal Lesions With Surveillance Via Mutation Analysis & Clinical Phenotype
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Predictive Cancer Model
Keywords: phenotype
surveillance
colonoscopy
colorectal neoplasia
genetic mutation
metachronous lesions
Lead sponsor: Military University Hospital, Prague
Sponsor class: OTHER
First posted: 2023-07-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with colorectal neoplasia detected in diagnostic colonoscopy.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 5 years
Secondary outcomes:
measure: Determination of the mutation profile colorectal lesions
timeFrame: 5 years
measure: Mutational profil of colorectal lesions
timeFrame: 5 years
Other outcomes:
measure: Mutational phenotype of patient.
timeFrame: 5 years
measure: Metachronous lesions
timeFrame: 5 years
measure: Similarity of the mutation profile of lesions found in the same area
timeFrame: 5 years
Locations:
city: Prague
country: Czechia
facility: Military University Hospital
Study officials:
affiliation: Military University Hospital, Prague
name: Stepan Suchanek, assoc. prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Biostatistics and Analyses Brno
name: Ondrej Ngo, Mgr.
role: STUDY_DIRECTOR
affiliation: Genomac Research Institute Prague
name: Lucie Benesova, RNDr.
role: STUDY_DIRECTOR
affiliation: Institute of Biostatistics and Analyses Brno
name: Ondrej Majek, RNDr.
role: STUDY_CHAIR
affiliation: Genomac Research Institute Prague
name: Tereza Halkova, Mgr.
role: STUDY_CHAIR
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