Ignite Creation Date:
2024-10-25 @ 7:52 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06625788
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-01
Brief Title:
Clinical and Endoscopic Characterization of Patients With Multiple Colorectal Adenomas A Multicenter Study in Spain ESPAPOLYP Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
CARACTERIZACIÓN CLÍNICA Y ENDOSCÓPICA DE PACIENTES CON MÚLTIPLES ADENOMAS COLORRECTALES ESPAPOLIP
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ESPAPOLYP
Brief Summary:
The aim is to clinically endoscopically and molecularly characterize patients with multiple colorectal adenomas establish the indication for genetic testing to rule out hereditary syndromes and identify the genes to be included and improve endoscopic screening recommendations for these patients and their relatives
Detailed Description:
HYPOTHESIS
Better characterization of patients with MAC multiple adenomatous colorectal polyps could help identify predictive factors of germline pathogenic variants
Identifying predictive factors of germline pathogenic variants would help optimize and standardize selection criteria for MAC patients to undergo genetic panel testing
The identification of extra-colonic manifestations in these patients would help implement relevant screening strategies
Studying the incidence of advanced neoplasia in surveillance colonoscopies in MAC patients would help optimize the intervals for endoscopic surveillance
Understanding the risk of developing CRC andor MAC in first-degree relatives of MAC patients without known germline pathogenic variants would allow the establishment of specific colorectal neoplasia screening in this population
The use of the FIT fecal immunochemical test in CRC andor MAC screening in first-degree relatives FDR of MAC patients could be useful by reducing the rate of unnecessary colonoscopies
OBJECTIVES
The project is subdivided into the following four subprojects
SUBPROJECT 1 GENPOLYP PROTOCOL
Objectives
To assess adherence to clinical practice guidelines for requesting genetic testing
To determine which clinical practice guideline is most used for requesting genetic testing
To establish the prevalence of germline pathogenic mutations in patients with MAP multiple adenomatous polyps
To evaluate predictive factors of germline pathogenic mutations in patients with MAP
SUBPROJECT 2 RE-SURVPOLYP
Objectives
Clinical characterization of the cohort To evaluate the prevalence of CRC and advanced neoplasia in patients with MAC To evaluate the prevalence of gastroduodenal manifestations To evaluate the prevalence of non-gastrointestinal manifestations To determine the need for colorectal surgery in MAC patients To assess the prevalence of CRC and advanced neoplasia in post-surgical surveillance
SUBPROJECT 3 PRO-SURVPOLYP
Objectives
To establish the post-polypectomy surveillance schedule based on the AEGSEMFYC guidelines
To assess the incidence of advanced neoplasia and CRC at 3 5 and 10 years To evaluate predictive factors of advanced neoplasia in surveillance colonoscopies
To assess CRC mortality at 5 and 10 years To assess the incidence of fundic gland polyps gastric adenomas duodenal adenomas and ampullary adenomas at 3 5 and 10 years
To assess the incidence of ampullary and duodenal adenocarcinoma at 3 5 and 10 years
To evaluate the prevalence of H pylori To establish screening indications for gastroduodenal lesions appropriate surveillance intervals and the endoscopic technique to be used
SUBPROJECT 4 FAMPOLYP Subproject 41 RE-FAMPOLYP
Objective
To describe the clinicopathological characteristics of the cohort To evaluate the prevalence of MAC in first-degree relatives FDRs of patients with multiple colorectal adenomas
To evaluate the prevalence of CRC in FDRs of MAC patients To evaluate the prevalence of variants of uncertain significance VUS coinciding between FDRs of patients with multiple colorectal adenomas for whom a multigene panel was requested
Subproject 42 PRO-FAMPOLYP
Objectives
To evaluate the incidence of CRC and advanced neoplasia in FDRs of patients with MAC under endoscopic surveillance at 5 years
To assess the incidence of MAC diagnosis in FDRs of patients with MAC under endoscopic surveillance at 5 years
To evaluate the diagnostic accuracy of the FIT test for CRC screening in FDRs of MAC patients
METHODOLOGY AND WORK PLAN
SUBPROJECT 1 GENPOLYP PROTOCOL Design Prospective multicenter observational study
Methodology
Patient Selection
In this protocol all patients who are detected with 10 adenomas in consecutive colonoscopies or a single colonoscopy andor surgical specimen if they have undergone colorectal surgery who have not previously undergone germline genetic testing via a multigene panel will be prospectively included Patients from families with a previously identified germline pathogenic mutation those with inflammatory bowel disease IBD and those with low performance status ECOG 3-4 will be excluded Patients who due to cognitive decline cannot make decisions may be included if their legal guardian authorizes their inclusion
In these patients a multigene panel test will be requested which must include the study of at least the following genes MLH1 MSH2 PMS2 MSH6 EPCAM APC MUTYH BMPR1A PTEN STK11 SMAD4 POLD POLE NTHL1 RNF43 BRCA1 BRCA2 GREM1
Variables to collect
The following variables will be collected
Demographics sex age race Clinical personal history of neoplasia type and age of diagnosis as well as treatment received comorbidities according to Charlson index weight height body mass index BMI abdominal circumference hypertension dyslipidemia diabetes mellitus
Medication use non-steroidal anti-inflammatory drugs NSAIDs acetylsalicylic acid ASA proton pump inhibitors PPIs calcium vitamin D
Dietary habits validated PREDIMED questionnaire Annex II smoking alcohol other drug use
Family history of neoplasia 1st and 2nd degree age of diagnosis type of neoplasia and degree of kinship Amsterdam II and Bethesda criteria will also be collected Annex III
Colonoscopy-related variables number of colonoscopies until diagnosis interval between colonoscopies number of adenomas and serrated lesions resected in each colonoscopy
Histological findings for each colonoscopy apart from the number of adenomas andor serrated polyps advanced adenomas 10 mm high-grade dysplasia or in situ adenocarcinoma advanced serrated lesions hyperplastic polyp 10 mm sessile serrated lesion 10 mm andor with dysplasia traditional serrated adenoma andor CRC will be specified If CRC is detected location TNM staging and results from the DNA repair protein system MMR immunohistochemistry will be recorded
Clinical practice guidelines used for genetic testing request Table 1 Genes included in the multigene panel and detected findings pathogenic mutations likely pathogenic mutations and variants of uncertain significance VUS will be described
Analysis of results
SPSS and MedCalc programs will be used to analyze the results A descriptive study will be conducted to report the prevalence of germline pathogenic mutations as well as adherence to clinical practice guidelines The cohort will then be divided into two groups patients with a germline pathogenic or likely pathogenic variant vs those without these variants Univariate logistic regression will be applied to assess predictive factors of pathogenic or likely pathogenic mutations and all variables with Plt01 will be included in a multivariate logistic regression analysis A significance level of Plt005 will be established
Better characterization of patients with MAC multiple adenomatous colorectal polyps could help identify predictive factors of germline pathogenic variants
Identifying predictive factors of germline pathogenic variants would help optimize and standardize selection criteria for MAC patients to undergo genetic panel testing
The identification of extra-colonic manifestations in these patients would help implement relevant screening strategies
Studying the incidence of advanced neoplasia in surveillance colonoscopies in MAC patients would help optimize the intervals for endoscopic surveillance
Understanding the risk of developing CRC andor MAC in first-degree relatives of MAC patients without known germline pathogenic variants would allow the establishment of specific colorectal neoplasia screening in this population
The use of the FIT fecal immunochemical test in CRC andor MAC screening in first-degree relatives FDR of MAC patients could be useful by reducing the rate of unnecessary colonoscopies
OBJECTIVES
The project is subdivided into the following four subprojects
SUBPROJECT 1 GENPOLYP PROTOCOL
Objectives
To assess adherence to clinical practice guidelines for requesting genetic testing
To determine which clinical practice guideline is most used for requesting genetic testing
To establish the prevalence of germline pathogenic mutations in patients with MAP multiple adenomatous polyps
To evaluate predictive factors of germline pathogenic mutations in patients with MAP
SUBPROJECT 2 RE-SURVPOLYP
Objectives
Clinical characterization of the cohort To evaluate the prevalence of CRC and advanced neoplasia in patients with MAC To evaluate the prevalence of gastroduodenal manifestations To evaluate the prevalence of non-gastrointestinal manifestations To determine the need for colorectal surgery in MAC patients To assess the prevalence of CRC and advanced neoplasia in post-surgical surveillance
SUBPROJECT 3 PRO-SURVPOLYP
Objectives
To establish the post-polypectomy surveillance schedule based on the AEGSEMFYC guidelines
To assess the incidence of advanced neoplasia and CRC at 3 5 and 10 years To evaluate predictive factors of advanced neoplasia in surveillance colonoscopies
To assess CRC mortality at 5 and 10 years To assess the incidence of fundic gland polyps gastric adenomas duodenal adenomas and ampullary adenomas at 3 5 and 10 years
To assess the incidence of ampullary and duodenal adenocarcinoma at 3 5 and 10 years
To evaluate the prevalence of H pylori To establish screening indications for gastroduodenal lesions appropriate surveillance intervals and the endoscopic technique to be used
SUBPROJECT 4 FAMPOLYP Subproject 41 RE-FAMPOLYP
Objective
To describe the clinicopathological characteristics of the cohort To evaluate the prevalence of MAC in first-degree relatives FDRs of patients with multiple colorectal adenomas
To evaluate the prevalence of CRC in FDRs of MAC patients To evaluate the prevalence of variants of uncertain significance VUS coinciding between FDRs of patients with multiple colorectal adenomas for whom a multigene panel was requested
Subproject 42 PRO-FAMPOLYP
Objectives
To evaluate the incidence of CRC and advanced neoplasia in FDRs of patients with MAC under endoscopic surveillance at 5 years
To assess the incidence of MAC diagnosis in FDRs of patients with MAC under endoscopic surveillance at 5 years
To evaluate the diagnostic accuracy of the FIT test for CRC screening in FDRs of MAC patients
METHODOLOGY AND WORK PLAN
SUBPROJECT 1 GENPOLYP PROTOCOL Design Prospective multicenter observational study
Methodology
Patient Selection
In this protocol all patients who are detected with 10 adenomas in consecutive colonoscopies or a single colonoscopy andor surgical specimen if they have undergone colorectal surgery who have not previously undergone germline genetic testing via a multigene panel will be prospectively included Patients from families with a previously identified germline pathogenic mutation those with inflammatory bowel disease IBD and those with low performance status ECOG 3-4 will be excluded Patients who due to cognitive decline cannot make decisions may be included if their legal guardian authorizes their inclusion
In these patients a multigene panel test will be requested which must include the study of at least the following genes MLH1 MSH2 PMS2 MSH6 EPCAM APC MUTYH BMPR1A PTEN STK11 SMAD4 POLD POLE NTHL1 RNF43 BRCA1 BRCA2 GREM1
Variables to collect
The following variables will be collected
Demographics sex age race Clinical personal history of neoplasia type and age of diagnosis as well as treatment received comorbidities according to Charlson index weight height body mass index BMI abdominal circumference hypertension dyslipidemia diabetes mellitus
Medication use non-steroidal anti-inflammatory drugs NSAIDs acetylsalicylic acid ASA proton pump inhibitors PPIs calcium vitamin D
Dietary habits validated PREDIMED questionnaire Annex II smoking alcohol other drug use
Family history of neoplasia 1st and 2nd degree age of diagnosis type of neoplasia and degree of kinship Amsterdam II and Bethesda criteria will also be collected Annex III
Colonoscopy-related variables number of colonoscopies until diagnosis interval between colonoscopies number of adenomas and serrated lesions resected in each colonoscopy
Histological findings for each colonoscopy apart from the number of adenomas andor serrated polyps advanced adenomas 10 mm high-grade dysplasia or in situ adenocarcinoma advanced serrated lesions hyperplastic polyp 10 mm sessile serrated lesion 10 mm andor with dysplasia traditional serrated adenoma andor CRC will be specified If CRC is detected location TNM staging and results from the DNA repair protein system MMR immunohistochemistry will be recorded
Clinical practice guidelines used for genetic testing request Table 1 Genes included in the multigene panel and detected findings pathogenic mutations likely pathogenic mutations and variants of uncertain significance VUS will be described
Analysis of results
SPSS and MedCalc programs will be used to analyze the results A descriptive study will be conducted to report the prevalence of germline pathogenic mutations as well as adherence to clinical practice guidelines The cohort will then be divided into two groups patients with a germline pathogenic or likely pathogenic variant vs those without these variants Univariate logistic regression will be applied to assess predictive factors of pathogenic or likely pathogenic mutations and all variables with Plt01 will be included in a multivariate logistic regression analysis A significance level of Plt005 will be established
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None