Clinical trial NCT05551416: The EpiGASTRIC/EDGAR Project: New Strategies for the Early Detection and Prevention of Gastric Cancer
Official title: Research and Development of New Strategies for the Early Detection and Prevention of Gastric Cancer in the Spanish Population: EpiGASTRIC/EDGAR Project.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gastric Neoplasms
Gastric Cancer
Gastric Lesion
Keywords: Gastric Cancer
Premalignant gastric lesions
Biomarkers
Prevalence
Endoscopy
Multiomics
Lead sponsor: Fundacion Miguel Servet
Sponsor class: OTHER
Collaborators: name: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain
name: Fundació Clínic per a la Recerca Biomèdica (FCRB), Spain
name: Miguel Servet Foundation/Navarrabiomed, Spain
name: Barcelona Clinic Hospital (HCB), Spain
name: Navarre University Hospital (HUN), Spain
name: Navarre Health Research Institute (IdiSNA), Spain
name: Carlos III Health Institute (ISCIII), Spain
name: Spanish Society of Digestive Endoscopy (SEED) Foundation
name: Spanish Association of Gastroenterology (AEG)
First posted: 2022-09-22
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: New strategies for gastric cancer (GC) early diagnosis
timeFrame: Up to 10 years
Secondary outcomes:
measure: Prevalence of premalignant gastric lesions (PGLs)
timeFrame: Up to 5 years
measure: Endoscopic characterization of PGLs
timeFrame: Up to 5 years
measure: Identification of GC hereditary predisposition by a customize multigene panel
timeFrame: Up to 5 years
measure: Identification of GC risk factors from clinical data and a lifestyle survey
timeFrame: Up to 5 years
measure: Discover and validation of new biomarkers for early diagnosis of GC
timeFrame: Up to 5 years
measure: Characterization of the microbiome: 16S rRNA studies
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Palma De Mallorca
country: Spain
facility: Hospital Comarcal de Inca
state: Baleares
city: Porto Cristo
country: Spain
facility: Hospital de Llevant
state: Baleares
city: Granollers
country: Spain
facility: Hospital General de Granollers
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Aranda De Duero
country: Spain
facility: Hospital Santos Reyes
state: Burgos
city: Mérida
country: Spain
facility: Hospital de Mérida
state: Extremadura
city: Ourense
country: Spain
facility: Hospital Universitario de Ourense
state: Galicia
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Gerona
country: Spain
facility: Hospital Josep Trueta
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References:
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.
citation: 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.