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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Gastric Neoplasms; Gastric Lesion
• Intervention / Treatment: Other: Identification of risk factors; Other: Identification of biomarkers; Other: Identification of gastric cancer hereditary predisposition; Other: Characterization of premalignant gastric lesions

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:

1. "EDGAR 1": symptomatic patients undergoing a diagnostic gastroscopy to study the prevalence of PGLs;
2. "EDGAR 2": PGLs and EGC with indication for endoscopic resection;
3. "EPIGASTRIC": patients diagnosed with GC;
4. 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 Type: Observational
• Enrollment (Estimated): 1200

Contacts and Locations

• Study Contact: Name: Leticia Moreira, MD, PhD; Phone Number: 2799 +34 932275400; Email: LMOREIRA@clinic.cat
• Study Contact Backup: Name: Eduardo Albéniz, MD, PhD; Phone Number: +34 848420370; Email: ealbenia@navarra.es

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Leticia Moreira; Email: LMOREIRA@clinic.cat
    • Sub-Investigator: Joan Llach
  • Burgos, Spain
    • Recruiting
    • Hospital Universitario de Burgos
    • Contact: Rosa M Saiz
    • Sub-Investigator: Gadea Hontoria
  • Gerona, Spain
    • Recruiting
    • Hospital Josep Trueta
    • Contact: Virginia Piñol
  • Zaragoza, Spain
    • Recruiting
    • Hospital Clinico Universitario Lozano Blesa
    • Contact: Gonzalo Hijos
    • Sub-Investigator: María José Domper
  • Zaragoza, Spain
    • Recruiting
    • Hospital Universitario Miguel Servet
    • Contact: María Elena Arruebo
  • Asturias
    • Oviedo, Asturias, Spain
      • Recruiting
      • Hospital Universitario Central de Asturias
      • Contact: Eva Barreiro
      • Sub-Investigator: Adolfo Suárez
      • Sub-Investigator: Pablo Florez
  • Baleares
    • Palma De Mallorca, Baleares, Spain
      • Recruiting
      • Hospital Comarcal de Inca
      • Contact: Silvia Patricia Ortega
    • Porto Cristo, Baleares, Spain
      • Recruiting
      • Hospital de Llevant
      • Contact: Gustavo O Patrón
  • Barcelona
    • Granollers, Barcelona, Spain
      • Recruiting
      • Hospital General de Granollers
      • Contact: Beatriz De Riba
    • Terrassa, Barcelona, Spain
      • Recruiting
      • Consorci Sanitari de Terrassa
      • Contact: Diana Zaffalon
  • Burgos
    • Aranda De Duero, Burgos, Spain
      • Recruiting
      • Hospital Santos Reyes
      • Contact: Luis Hernández
      • Sub-Investigator: Raquel Grajal
  • Extremadura
    • Mérida, Extremadura, Spain
      • Recruiting
      • Hospital de Mérida
      • Contact: Pedro Delgado
  • Galicia
    • Ourense, Galicia, Spain
      • Recruiting
      • Hospital Universitario de Ourense
      • Contact: Sara Zarraquiños
  • Madrid
    • Majadahonda, Madrid, Spain
      • Recruiting
      • Hospital Puerta de Hierro
      • Contact: Alberto Herreros de Tejada
  • Navarra
    • Pamplona, Navarra, Spain
      • Recruiting
      • Hospital Universitario de Navarra
      • Contact: Eduardo Albéniz; Email: ealbenia@navarra.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This cohort study is designed to enroll the Spanish population patients who are diagnosed gastric cancer; symptomatic patients subjected to a diagnostic gastroscopy who have or not premalignant gastric lesions and early gastric neoplasias susceptible to be treated by endoscopy resection; and healthy control participants by multicenter-prospective registry. Nevertheless, the study will be open to international participation.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	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: Identification of biomarkers; Multiomic 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
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: Identification of biomarkers; Multiomic 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New strategies for gastric cancer (GC) early diagnosis	Prediction of risk factors and identification of new strategies for an early diagnosis of GC.	Up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of premalignant gastric lesions (PGLs)	Determine the prevalence of PGLs in the EDGAR 1 cohort.	Up to 5 years
Endoscopic characterization of PGLs	Identification and characterization of PGLs through high definition endoscopic study, testing the concordance between endoscopic and histological classifications.	Up to 5 years
Identification of GC hereditary predisposition by a customize multigene panel	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.	Up to 5 years
Identification of GC risk factors from clinical data and a lifestyle survey	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.	Up to 5 years
Discover and validation of new biomarkers for early diagnosis of GC	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.	Up to 5 years
Characterization of the microbiome: 16S rRNA studies	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.	Up to 5 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Herrera-Pariente C, Montori S, Llach J, Bofill A, Albeniz E, Moreira L. Biomarkers for Gastric Cancer Screening and Early Diagnosis. Biomedicines. 2021 Oct 12;9(10):1448. doi: 10.3390/biomedicines9101448.
• Herrera-Pariente C, Capo-Garcia R, Diaz-Gay M, Carballal S, Munoz J, Llach J, Sanchez A, Bonjoch L, Arnau-Collell C, Soares de Lima Y, Golubicki M, Jung G, Lozano JJ, Castells A, Balaguer F, Bujanda L, Castellvi-Bel S, Moreira L. Identification of New Genes Involved in Germline Predisposition to Early-Onset Gastric Cancer. Int J Mol Sci. 2021 Jan 28;22(3):1310. doi: 10.3390/ijms22031310.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Prevalence; Gastric Cancer; Endoscopy; Biomarkers; Multiomics; Premalignant gastric lesions
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: HCB/2021/0482-PI_2021/76

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