InteGRAtive Analysis of tuMor, Microenvironment, immunitY and Patient Expectation for Personalized Response Prediction in Gastric Cancer

Study Overview
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Brief Summary
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Multicentric, exploratory, non-pharmacologic, retrospective/prospective, translational study aiming to identify the molecular, cellular and psychological-sociological variables predictive of response to chemotherapy in gastric cancer patients.

Detailed Description
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Gastric cancer (GC) is a complex disease that represents the fifth most common malignancy in the world and the third leading cause of cancer death in both sexes. Chemotherapy (CT) combined with surgery represents the standard of care for stages II-III GC, but the efficacy of such treatments is still limited for many patients. It is mandatory to develop novel strategies aimed at identifying predictive markers, as well as deciphering the impact of the psychological-social and cultural environment of each patient on the outcome. GRAMMY study proposes a novel interdisciplinary approach integrating high impact basic, translational and psychological/sociological research towards developing an optimized patient stratification tool for the early prediction of therapy-resistant GC patient groups.

Official Title
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InteGRAtive Analysis of tuMor, Microenvironment, immunitY and Patient Expectation for Personalized Response Prediction in Gastric Cancer

Conditions
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Gastric Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with diagnosis of histologically confirmed, potentially resectable adenocarcinoma of the stomach (GC) or the gastric-esophageal junction (GEJ) treated with the standard regimens (5-Fluoro-Uracil or Capecitabine + Oxaliplatin +/- Docetaxel) Participant is willing and able to give informed consent for participation in the study (prospective and retrospective cohort) or Substitutive Informed Consent Declaration Form will be subscribed by the PI for patients that are not reachable Male or Female, aged >18 years Availability of tissue samples and clinico-pathological data for retrospective cohort Exclusion Criteria: Age < 18 years Early Gastric Cancer and T2 (if N0) Linitis plastica Positive peritoneal cytology or peritoneal involvement Distant metastases Patient refusal to participate Patient refusal to the use of their own samples for research Patient withdrawing from treatment plan whilst under therapy due to patient co-morbidities or failure to comply with clinical counselling Patients with underlying pathologies rendering sampling of biological material either as endangering patient's clinical status or as unusable Patients with mental illness hindering the capacity to provide precise information in questionnaires or successfully comply with caregiver's recommendations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gastric cancer patients<br>gastric cancer patients with histologically confirmed, potentially resectable adenocarcinoma of the stomach or the gastroesophageal junction receiving the standard of medical care in Europe | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genomic alterations in tumoral tissue in responders and non-responders | Number of Genomic alterations in tumoral tissue | 36 months | 
| Quantitative and qualitative analysis of the tumor microenvironment composition in responders and non-responders | Analysis of type and size of immune cell subpopulations surrounding primary tumor and extracellular matrix composition on FFPE samples collected at diagnosis and/or surgery. Correlation of data acquired to Participant's response score (TRG or DFS). | 36 months | 
| Analysis of cell-free DNA (cfDNA) from blood samples in responders and non-responders | cfDNA will be quantified in Participant's peripheral blood derivatives (plasma, serum) and characterized for Genomic alterations. Samples will be obtained (1) prior to and (2) by completion of chemotherapy in the Neoadjuvant Chemotherapy (NCT) treated cohorts, together with sampling after surgery (3). TRG score will be utilized as measure of response. Accordingly, in NCT-naive cohorts, analysis of samples obtained 1) pre- operatively and 2) by completion of post-operative chemotherapy treatment will be correlated with the respective Disease-Progression clinical indicators. | 36 months | 
| Analysis of circulating tumor cells (CTC) from blood samples in responders and non-responders. | gene expression profile of CTC cells (when isolated in sufficient quantity) | 36 months | 
| Peripheral blood mononuclear cells (PBMCs) and host immunity parameters in responders and non-responders | Phenotype analysis of representative immune cell subpopulations (i.e. monocytes, helper T cells, cytotoxic T cells, Tregs, Natural Killer (NK) /NKT) in Participants' peripheral blood samples obtained prior- and post- treatment. Combinational analysis of data acquired in correlation with Patient's response score. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychological status of patients in relation to therapy response | Psychological status of patients in relation to therapy response evaluated by a psychologist through structured interview | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric cancer, Chemotherapy, Response, Personalized medicine