An observational study in Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma (Siewert II-III), sponsored by Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-09.
Sponsored by Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis · Observational
Surgical resection remains the only curative option for resectable gastric cancer, but perioperative FLOT chemotherapy is associated with substantial rates of chemoresistance and recurrence, largely driven by marked tumor heterogeneity. Recent data from the MATTERHORN phase III trial have shown that adding durvalumab to perioperative FLOT improves pathological complete response and survival, supporting this combination as a new standard of care for resectable gastric and gastroesophageal junction adenocarcinoma.
This observational multicenter study aims to characterize angiogenic and immune profiles within the tumor microenvironment and peripheral blood, in order to identify cellular and molecular signatures associated with response or resistance to perioperative FLOT plus durvalumab. Longitudinal biospecimen collection (PBMCs, serum, plasma, endoscopic biopsies, surgical specimens) will be integrated with multiparametric flow cytometry, single-cell transcriptomics and TCR/BCR sequencing, immunohistochemistry, pathomics and multiplex immunoassays, to provide mechanistic insights and potential predictive biomarkers.
This observational multicenter study will prospectively enroll approximately 250 patients with operable, locally advanced gastric or gastroesophageal junction adenocarcinoma who receive perioperative FLOT plus durvalumab according to current clinical practice. Patients typically present with locally advanced disease (T ≥2 and/or node-positive) as defined by the AJCC 8th edition, and are candidates for perioperative chemo-immunotherapy followed by surgery.
Peripheral blood samples for PBMC isolation and serum/plasma storage will be obtained at baseline before neoadjuvant treatment (N1), before surgery (N2), and approximately 2 months after completion of adjuvant therapy (N3). Tumor tissue will be collected through diagnostic endoscopic biopsies and surgical resections; fresh and FFPE specimens will be used for immunohistochemistry, pathomics and omics analyses, including organoid cultures.
The study will implement a multiparametric registry integrating clinical, imaging and omics data, ensuring harmonized data collection across the two IRCCS centers (IRCCS Saverio de Bellis and Humanitas Clinical and Research Center). Tumor-infiltrating lymphocytes and PBMCs will be profiled by spectral flow cytometry (up to 40 markers), single-cell RNA sequencing and TCR/BCR sequencing to define immune subsets, activation and exhaustion states, and clonal expansion patterns.
Whole-slide digital histology (HE-stained sections) will be analyzed to derive robust pathomic biomarkers related to vascular architecture and immune cell distribution, previously associated with response to anti-angiogenic therapies; these biomarkers will be validated in the perioperative gastric/GEJ cohort. Serum cytokine and chemokine panels will be assessed using Luminex xMAP technology, while CT imaging acquired for staging and follow-up will be annotated to calibrate mathematical models predicting treatment response.
Statistical analyses will treat this project as a pilot study, given the lack of previous evidence on predictors of complete response to perioperative therapy. Patients will be stratified by Tumor Regression Grade (TRG), with TRG 1-2 considered responders and TRG 3-4 non-responders, and effect-size measures, ensemble machine-learning algorithms and multilevel longitudinal models will be used to identify and evaluate angiogenic and immune markers associated with short-term outcomes.
Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis is the lead sponsor of 55 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adult patients (age >= 18 years) with histologically confirmed, operable, locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, candidate to perioperative treatment with FLOT plus durvalumab at the participating IRCCS centers. Patients are enrolled consecutively as they start perioperative treatment in clinical practice.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with operable, locally advanced gastric or gastroesophageal junction adenocarcinoma receiving perioperative chemotherapy (FLOT regimen: docetaxel, oxaliplatin, leucovorin, 5-fluorouracil) combined with durvalumab (anti-PD-L1) as standard of care. Longitudinal biological samples (peripheral blood and tumor tissue) are collected for molecular characterization of tumor-microenvironment interactions and identification of predictive biomarkers of pharmacological resistance.
This study also gives Durvalumab. No intervention listed here names it: that was found by reading the record.
Identification of immune and angiogenic cellular subsets associated with pathological response to perioperative FLOT plus durvalumab
Identification of specific cellular subsets and activation/exhaustion states, assessed by scRNA-seq, TCR/BCR sequencing, and multiparametric spectral flow cytometry of tumor-infiltrating lymphocytes (TILs) and PBMCs, associated with pathological response (Tumor Regression Grade TRG 1-2) or resistance (TRG 3-4) to perioperative FLOT plus durvalumab.
Time frame: At surgical resection (approx. 3-4 months after treatment initiation) and approx. 2 months after completion of adjuvant therapy
Association between angiogenic and immune signatures and clinical outcomes
Correlation of angiogenic and immune profiles (serum cytokine/chemokine panels by Luminex xMAP, pathomic biomarkers from whole-slide HE images, and flow cytometry data) with clinical outcomes including Tumor Regression Grade (TRG), early recurrence, and short-term survival.
Time frame: From baseline to approximately 2 months after completion of adjuvant therapy (up to approximately 9 months)
Validation of a pathomic biomarker related to angiogenesis and immune response
Validation of a previously developed pathomic biomarker derived from whole-slide HE digital histology, related to vascular architecture and immune cell spatial distribution, as a predictor of response to perioperative FLOT plus durvalumab in gastric and GEJ adenocarcinoma.
Time frame: At baseline (endoscopic biopsy) and at surgical resection (approximately 3-4 months after treatment initiation)
Characterization of immune evasion mechanisms in non-responders
Characterization of immune evasion mechanisms in the tumor microenvironment of non-responders (TRG 3-4) based on single-cell analyses (scRNA-seq, TCR/BCR-seq) of TILs and PBMCs, including identification of exhausted T cell populations, immunosuppressive cell subsets, and altered antigen presentation pathways.
Time frame: At surgical resection (approx. 3-4 months after treatment initiation) and approx. 2 months after completion of adjuvant therapy
No study locations are listed for this record.
Plan to share: No
Start is estimated for Sep 2026; primary completion for Sep 2027, 12 months later.
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This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis