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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05551416
• Other study ID #: HCB/2021/0482-PI_2021/76
• Status: Recruiting
• Start date: September 9, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2023
• Source: Fundacion Miguel Servet
• Contact: Leticia Moreira, MD, PhD
• Phone: +34 932275400
• Email: LMOREIRA[@]clinic.cat
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Cancer
• Gastric Lesion
• Gastric Neoplasms
• Stomach Neoplasms

Intervention

Other:
• Identification of risk factors
Demographics, life habits and risk factors studies
• Characterization of premalignant gastric lesions
Identification and characterization of premalignant gastric lesions through high definition endoscopic study. Concordance between endoscopic and histological classifications
• Identification of biomarkers
Multiomic studies
• Identification of gastric cancer hereditary predisposition
Genomic studies for the identification of individuals with hereditary GC predisposition

Locations

Country	Name	City	State
Spain	Hospital Santos Reyes	Aranda De Duero	Burgos
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital Josep Trueta	Gerona
Spain	Hospital General de Granollers	Granollers	Barcelona
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital de Mérida	Mérida	Extremadura
Spain	Hospital Universitario de Ourense	Ourense	Galicia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Comarcal de Inca	Palma De Mallorca	Baleares
Spain	Hospital Universitario de Navarra	Pamplona	Navarra
Spain	Hospital de Llevant	Porto Cristo	Baleares
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (10)

Lead Sponsor

Collaborator

EDUARDO ALBENIZ

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

Country where clinical trial is conducted

Spain, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Prevalence of premalignant gastric lesions (PGLs)	Determine the prevalence of PGLs in the EDGAR 1 cohort.	Up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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