Clinical Study of Taurine Combined With Neoadjuvant Chemo-Immunotherapy for Treatment of Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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This project aims to evaluate the efficacy and safety of oral taurine supplementation combined with PD-1 inhibitor (serplulimab) and chemotherapy in inducing systemic CD8+ T cell responses and achieving improved gastric cancer patient outcomes than with serplulimab and chemotherapy alone.

Official Title
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A Prospective, Randomized Controlled Clinical Study of The Efficacy and Safety of Taurine Combined With Serplulimab and Chemotherapy Versus Serplulimab Combined With Chemotherapy for Treatment of Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Cancer

Intervention / Treatment
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* Dietary Supplement: Taurine
* Biological: Serplulimab
* Drug: XELOX regimen
* Drug: FLOT regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years old, no gender limitation; Pathologically confirmed gastric or gastroesophageal junction adenocarcinoma with cTNM stage II/III; Expected survival of ≥ 3 months; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Patients informed about the purpose and course of the study and provided a written consent to participate. Exclusion Criteria: Use of taurine agent within 1 month prior to the first dose of study treatment and throughout the study; Patients with positive HER-2 and willing to receive herceptin treatment; Patients with gastrointestinal obstruction or active bleeding in the gastrointestinal tract, as well as perforation and dysphagia; Patients with severe heart, lung, liver, kidney, endocrine, hematopoietic system or psychiatric diseases were considered not suitable for the study group; Patients with other medical conditions that interfere with the trial and are deemed unsuitable for inclusion in the trial by the investigator; Other conditions that the investigator thinks are not suitable to participate in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized controlled clinical study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Taurine + Serplulimab + investigator's choice chemotherapy<br>Taurine + Serplulimab + XELOX or Taurine + Serplulimab + FLOT | Dietary Supplement: Taurine<br>* Taurine supplementation in capsules of 1.0 gram of taurine powder. Dosage: 2.0 gram/day. Frequency: 2 time/day.<br>Biological: Serplulimab<br>* Serplulimab<br>Drug: XELOX regimen<br>* Oxaliplatin + capecitabine<br>Drug: FLOT regimen<br>* Fluorouracil + leucovorin + oxaliplatin + docetaxel<br>|
| Active Comparator: Serplulimab + investigator's choice chemotherapy<br>Serplulimab + XELOX or Serplulimab + FLOT | Biological: Serplulimab<br>* Serplulimab<br>Drug: XELOX regimen<br>* Oxaliplatin + capecitabine<br>Drug: FLOT regimen<br>* Fluorouracil + leucovorin + oxaliplatin + docetaxel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response | To evaluate the pathologic complete response rate of locally advanced gastric cancer treated with concurrent serplulimab with chemotherapy with or without taurine supplementation. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | The surgical margin is microscopically-negative for residual tumor. | Through study completion, an average of 1 year | 
| Major pathological response (MPR) | Residual tumor cells below 10% in the resected specimen. | Through study completion, an average of 1 year | 
| Disease-free survival (DFS) | DFS was defined as the time from surgery to postoperative recurrence or death from any cause, whichever occurred first. DFS was censored on the last tumor assessment date for patients still alive and without recurrence. | Through study completion, an average of 1 year | 
| Event-free survival (EFS) | EFS was the time from enrollment to recurrence or death from any cause. EFS was censored on the last tumor assessment date for patients still alive and without recurrence. | Through study completion, an average of 1 year | 
| Overall survival (OS) | OS was the time from enrolment to death from any cause. OS was censored on the last date known to be alive for patients without documentation of death. | Through study completion, an average of 1 year | 
| Changes in CD8+ T cell infiltration in tumor tissue | Changes in number, effector (TNF-α, IFN-γ, etc.) production and immune checkpoint molecule (PD-1, CTLA-4, etc.) expression of tumor-infiltrating CD8+ T cells in gastric cancer endoscopic biopsy or surgical resection material assessed via flow cytometry and immunohistochemistry. | 1 year | 
| Changes in CD8+ T cell death and function | Changes in number, apoptosis rate, effector (TNF-α, IFN-γ, etc.) production and immune checkpoint molecule (PD-1, CTLA-4, etc.) expression of CD8+ T cells in peripheral venous blood assessed via flow cytometry. | Through study completion, an average of 1 year | 
| Safety endpoints | Number of study subjects experiencing adverse events (AEs), dose-limiting toxicities, and serious adverse events (SAEs). Safety profile will be assessed through laboratory evaluations, vital signs, and physical examinations. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Taurine, neoadjuvant immunotherapy and chemotherapy