The EpiGASTRIC/EDGAR Project: New Strategies for the Early Detection and Prevention of Gastric Cancer

Sponsor

EDUARDO ALBENIZ (Other)

Overall Status

Recruiting

CT.gov ID

NCT05551416

Collaborator

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain (Other), Fundació Clínic per a la Recerca Biomèdica (FCRB), Spain (Other), Miguel Servet Foundation/Navarrabiomed, Spain (Other), Barcelona Clinic Hospital (HCB), Spain (Other), Navarre University Hospital (HUN), Spain (Other), Navarre Health Research Institute (IdiSNA), Spain (Other), Carlos III Health Institute (ISCIII), Spain (Other), Spanish Society of Digestive Endoscopy (SEED) Foundation (Other), Spanish Association of Gastroenterology (AEG) (Other)

1,200

Enrollment

Locations

63.7

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a multicenter, prospective cohort study, which are planned to enroll at least 600 patients who diagnosed the primary gastric cancer (GC); around 50 patients with premalignant gastric lesions (PGLs) and early gastric neoplasias (EGC) treated by endoscopy resection; and no less than 600 healthy normal cohort participants, for more than 18 months in the Spanish population. All participants who enrolled in this registry will be questioned by the life habits survey; and clinical data and biological samples of these participants were analyzed in order to look for new diagnostic tools.

The aim of this study is to evaluate clinical, endoscopic and molecular approaches to identify individuals with high-risk of GC. Thus, it would be allow the adoption of preventive measures to reduce mortality through early detection and/or the reduction of its incidence.

Condition or Disease	Intervention/Treatment	Phase
Gastric Neoplasms Gastric Cancer Gastric Lesion	Other: Identification of risk factors Other: Characterization of premalignant gastric lesions Other: Identification of biomarkers Other: Identification of gastric cancer hereditary predisposition

Detailed Description

Gastric cancer (GC) is the fifth most common and the third more deadly cancer in the world. In Spain, the incidence is 7.8 cases per 100,000 inhabitants, being twice as frequent in men as in women. During 2020, 7.577 new cases were diagnosed and approximately 5201 deaths occurred (Spanish association against cancer, AECC). Most cases are diagnosed in an advanced stage with a 5-year survival rate lower than 30%, which highlights the great importance of an early diagnosis.

Thus, this study aims to evaluate clinical, endoscopic and molecular approaches to identify individuals with high-risk of GC.

Methods: Coordinate and prospective project that considers the gender dimension of population-based study within a collaborative network. It includes different but interrelated cohorts:

"EDGAR 1": symptomatic patients undergoing a diagnostic gastroscopy to study the prevalence of PGLs;
"EDGAR 2": PGLs and EGC with indication for endoscopic resection;
"EPIGASTRIC": patients diagnosed with GC;
CONTROLS: patients without gastric pathology or a familial history of GC, obtained from the cohort EDGAR1.

Although GC diagnosis has been characterized by endoscopy, there has been a strong demand for low or non-invasive methods of GC detection. In this sense, clinical information and biological samples obtained by less invasive methods will be collected prospectively from the participating centers. State-of-the-art high-definition endoscopy and multiomic techniques will be used to perform:

Clinical studies: Study the prevalence of GC and PGLs and genetic and environmental predisposing factors. Evaluation of high-definition endoscopy efficacy in the detection of PGLs and EGC. Concordance between endoscopic and histological classifications of PGLs. Estimate the risk of PGLs progression according to the follow-up of the lesions. Identification of GC-high-risk individuals, based on clinical data, familial factors, PGLs and a life habits survey.
Translational studies: Identify and validate nucleic acids and proteins as new biomarkers of GC and PGLs in biological samples obtained by low or non-invasive methods and comparison with those obtained from histological samples and with the traditional markers used in GC diagnosis.

Given the multicenter nature of this project, standard operating procedures (SOPs) have also been established for the collection, processing, storage, and management of biological samples, so that it is carried out in the same way in all participating centers.

The data will be collected on the REDCap-AEG online platform, which can be accessed by researchers from each center through an identification code, respecting the current Organic Law on Data Protection. For patient registries, a specific database has been designed for each subproject (EDGAR 1, EDGAR 2 and EPIGASTRIC). This guarantees the quality of the data and allows its verification, as it defines, classifies and illustrates the different parameters to be assessed by the participating researchers. Finally, it allows the codification and anonymization of the data entered, which guarantees compliance with the data protection law of this study.

Statistical analysis: The SPSS program (IBM, NY) and/or the R software (https://www.r-project.org/) will be used. The differences between qualitative variables will be compared using Fisher's test. The quantitative variables will be analyzed using a non-parametric test (Mann-Whitney or Kruskall-Wallis for unpaired samples and Wilcoxon for paired samples). A "p" value <0.05 will be considered statistically significant. All the registered variables will be studied to determine their association with the diagnosis by means of univariate and multivariate logistic regression analysis. In addition, through an interaction study, we will evaluate whether there are risk factors associated with the presence/prognosis of lesions that differentially affect subgroups of patients.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Research and Development of New Strategies for the Early Detection and Prevention of Gastric Cancer in the Spanish Population: EpiGASTRIC/EDGAR Project.

Actual Study Start Date :

Sep 9, 2021

Anticipated Primary Completion Date :

Sep 30, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
EPIGASTRIC Patients with GC.	Other: Identification of risk factors Demographics, life habits and risk factors studies Other: Identification of biomarkers Multiomic studies Other: Identification of gastric cancer hereditary predisposition Genomic studies for the identification of individuals with hereditary GC predisposition
EDGAR 1 Symptomatic patients subjected to a diagnostic gastroscopy to study the prevalence of premalignant gastric lesions.	Other: Identification of risk factors Demographics, life habits and risk factors studies Other: Characterization of premalignant gastric lesions Identification and characterization of premalignant gastric lesions through high definition endoscopic study. Concordance between endoscopic and histological classifications Other: Identification of biomarkers Multiomic studies
EDGAR 2 Patients with premalignant gastric lesions and early gastric neoplasias treated by endoscopy resection.	Other: Identification of risk factors Demographics, life habits and risk factors studies Other: Characterization of premalignant gastric lesions Identification and characterization of premalignant gastric lesions through high definition endoscopic study. Concordance between endoscopic and histological classifications Other: Identification of biomarkers Multiomic studies
Negative control Patients from "EDGAR 1" without gastric pathology or familial history of this neoplasia.	Other: Identification of risk factors Demographics, life habits and risk factors studies Other: Identification of biomarkers Multiomic studies

Outcome Measures

Primary Outcome Measures

New strategies for gastric cancer (GC) early diagnosis [Up to 10 years]
Prediction of risk factors and identification of new strategies for an early diagnosis of GC.

Secondary Outcome Measures

Prevalence of premalignant gastric lesions (PGLs) [Up to 5 years]
Determine the prevalence of PGLs in the EDGAR 1 cohort.
Endoscopic characterization of PGLs [Up to 5 years]
Identification and characterization of PGLs through high definition endoscopic study, testing the concordance between endoscopic and histological classifications.
Identification of GC hereditary predisposition by a customize multigene panel [Up to 5 years]
Define de most effective strategy for the identification of individuals with hereditary GC predisposition. In order to perform a clinical validation of the candidate genes identified by whole exome sequencing according to previous results of the research team (Herrera-Pariente, et al. IJMS 2021), a customize multigene panel has been designed including 25 potentially germline genetic variants associated to hereditary GC and 13 genes already associated with a higher risk of GC. This panel has been already tested, by the research group, ensuring its viability.
Identification of GC risk factors from clinical data and a lifestyle survey [Up to 5 years]
Based on the endoscopic classifications of the lesions found, the demographic data of the patient and their lifestyle and diet habits obtained through a specific questionnaire, risk factors involved in the development of CG will be identified through logistic regression. The identified risk factors will be used to create a predictive model.
Discover and validation of new biomarkers for early diagnosis of GC [Up to 5 years]
Multiomic data analysis of solid and liquid biopsies of the different cohorts in order to discover new molecules susceptible to be used as early diagnosis biomarkers. Validate them as screening test of GC.
Characterization of the microbiome: 16S rRNA studies [Up to 5 years]
The DNA extracted in the different cohorts is subjected to 16S rRNA gene-targeted sequencing to validate this microbial composition profile as a candidate for a noninvasive GC screening test.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults over 18 years-old.
EDGAR 1 cohort: symptomatic patients undergoing a diagnostic gastroscopy for a prevalence study of PGLs.
EDGAR 2 cohort: PGLs and early GC with indication for endoscopic resection.
EPIGASTRIC cohort: patients diagnosed with GC.
CONTROL cohort: patients without gastric pathology or a familial history of GC, obtained from the EDGAR 1.

Exclusion Criteria:

Refusal of the patient to participate in the study.
Medical, psychological or legal inability of the patient to enter the study.
EDGAR1: Previous diagnosis of PGLs, previous gastric surgery, contraindication for gastroscopy or taking biopsies.
EDGAR 2: Contraindication for resection/biopsy.
EPIGASTRIC: gastric neoplasm other than adenocarcinoma.

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain
2	Hospital Comarcal de Inca	Palma De Mallorca	Baleares	Spain
3	Hospital de Llevant	Porto Cristo	Baleares	Spain
4	Hospital General de Granollers	Granollers	Barcelona	Spain
5	Consorci Sanitari de Terrassa	Terrassa	Barcelona	Spain
6	Hospital Santos Reyes	Aranda De Duero	Burgos	Spain
7	Hospital de Mérida	Mérida	Extremadura	Spain
8	Hospital Universitario de Ourense	Ourense	Galicia	Spain
9	Hospital Puerta de Hierro	Majadahonda	Madrid	Spain
10	Hospital Universitario de Navarra	Pamplona	Navarra	Spain
11	Hospital Clínic de Barcelona	Barcelona		Spain
12	Hospital Universitario de Burgos	Burgos		Spain
13	Hospital Josep Trueta	Gerona		Spain
14	Hospital Clínico Universitario Lozano Blesa	Zaragoza		Spain
15	Hospital Universitario Miguel Servet	Zaragoza		Spain