Clinical trial NCT04015466: Advanced GC Multi-omic Characterization in EU and CELAC Populations
Official title: Advanced GC Multi-omic Characterization in EU and CELAC Populations
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastric Cancer
Keywords: Gastric Cancer
Personalized medicine
Oncology
Solid tumor
Primary Intervention
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
Collaborators: name: Instituto Nacional de Cancerologia de Mexico
name: Amsterdam UMC, location VUmc
name: Pontificia Universidad Catolica de Chile
name: Vall d'Hebron Institute of Oncology
name: INSTITUTO ALEXANDER FLEMING
name: Hospital Central del IPS
name: IPATIMUP - Instituto De Patologia E Imunologia Molecular Da Universidade Do Porto
First posted: 2019-07-11
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: * Subjects \>18 years old, with high diagnostic suspicion of advanced GC diagnosis (Stage III and IV)
* Subjects \>18 years old to whom a gastroscopy was indicated and confirmed absent of GC.

Brief summary: Observational study (cohort type) of advanced GC patients that will be recruited prospectively to study biological factors associated with the disease and relevant clinical outcomes.

Detailed description: Despite of multiple attempts to improve treatment in recent decades, none strategies has improved prognosis in locally advanced stage III and IV GC. A therapeutic approach to GC based on current histological and image criteria (Tumour Node Metastasis -TNM- stage) is insufficient. Although multiple targeted agents are currently under investigation, so far, only trastuzumab and ramucirumab have demonstrated efficacy in advanced GC and have a regulatory approval. For this reason, the identification of specific targets that could be susceptible for drug inhibition, is an urgent requirement. Moreover, most studies and current international databases on late-stage/advanced GC are largely based on Asian populations, in sharp contrast tumour biology and genome of EU or CELAC populations remain poorly known.

The primary objective of this study are to:

1. Characterize a multi-centric cohort including EU and CELAC populations diagnosed with advanced GC through a multi-omic approach including proteomics, genomics, transcriptomics, microbiome and exposome analysis due to study the determinants of GC.
2. Identify the regional differences in EU and CELAC populations recruiting patients for this study for each omic characterization due to identify the high-risk group populations.
3. Identify and select from the multi-omic approach those biomarkers useful for the development of an algorithm to guide the therapeutic approach for advanced GC.

Eligibility criteria: Cases:

* Inclusion criteria:

  * Subjects ≥18 years old.
  * GC diagnosis stages III and IV (including gastroesophageal junction cancer) and/or a gastroscopy indication due to the high diagnostic suspicion of GC as part of the study of his disease.
  * Has given and signed the IC to participate in this study.
* Exclusion criteria:

  • Patients diagnosed with GC early disease (stage I and II) suitable for resectable strategy.
* Withdrawal criteria:

  * Patients initially recruited with high suspicion of GC diagnosis but not confirmed by the pathological report.

Controls:

* Inclusion criteria (only for microbiome analysis):

  * Subjects ≥18 years old.
  * Subjects to whom a gastroscopy is indicated within clinical care and is confirmed absent of GC in the same centres will be matched in age (+/- 10 years), gender and pertaining from the same region of the GC case.
  * Has given and signed the IC to participate in this study.
* Exclusion criteria:

  * Subjects from a different geographic area from the cases.
  * Patients with high suspicion of GC.
  * Patients with previous histopathologic diagnosis of peptic (gastric or duodenal) ulcer disease and/or atrophy or intestinal metaplasia.
  * Patients that have received antimicrobials during the 4 weeks period prior to the endoscopy.
  * Patients that have received proton pump inhibitors or H2-receptor antagonists, at least 2 weeks prior to the endoscopy

Primary outcomes:
measure: Development of a new diagnostic algorithm for gastric cancer that includes molecular landscape, patient history, histopathological and environmental factors, personal microbiome and immune landscape
timeFrame: 3 years
Secondary outcomes:
measure: Proteomic analysis of gastric cancer tissue
timeFrame: 3 years
measure: Genomics (tumour next-generation sequencing)
timeFrame: 3 years
measure: Transcriptomics (Nanostring immune gene expression panel)
timeFrame: 3 years
measure: Microbiota sequencing (including level of Epstein-Barr virus [EBV] DNA)
timeFrame: 3 years
measure: Dietary habits as assessed by a new study-specific questionnaire
timeFrame: 3 years
measure: Biological risk factors as assessed through medical chart review
timeFrame: 3 years
measure: Daily routines as assessed by a new study-specific questionnaire
timeFrame: 3 years
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Santiago
country: Chile
facility: Pontificia Universidad Católica de Chile
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerología de México
city: Amsterdam
country: Netherlands
facility: VU Medical Centre
city: Asunción
country: Paraguay
facility: GenPat
city: Porto
country: Portugal
facility: Institute of Pathology and Immunology of University of Porto
city: Barcelona
country: Spain
facility: Vall d'Hebron Institut d'Oncologia
city: Valencia
country: Spain
facility: Hospital Clínico Univeristario de Valencia
Study officials:
References:
citation: van Schooten TS, Derks S, Jimenez-Marti E, Carneiro F, Figueiredo C, Ruiz E, Alsina M, Molero C, Garrido M, Riquelme A, Caballero C, Lezcano E, O'Connor JM, Esteso F, Farres J, Mas JM, Lordick F, Vogt J, Cardone A, Girvalaki C, Cervantes A, Fleitas T; members of LEGACy consortium. The LEGACy study: a European and Latin American consortium to identify risk factors and molecular phenotypes in gastric cancer to improve prevention strategies and personalized clinical decision making globally. BMC Cancer. 2022 Jun 13;22(1):646. doi: 10.1186/s12885-022-09689-9.