Gastric Cancer
Conditions
Keywords
Taurine, neoadjuvant immunotherapy and chemotherapy
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTTaurine
Taurine supplementation in tablets of 1.0 gram of taurine powder. Dosage: 3.0 gram/day. Frequency: 3 time/day.
BIOLOGICALSerplulimab
Serplulimab
DRUGXELOX regimen
Oxaliplatin + capecitabine
DIETARY_SUPPLEMENTPlacebo
Taurine placebo in tablets of 1.0 gram of starch powder. Dosage: 3.0 gram/day. Frequency: 3 time/day.
Sponsors
Tang-Du Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Prospective, multicenter, double-blind, randomized controlled clinical study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years old, no gender limitation; 2. Pathologically confirmed gastric or gastroesophageal junction adenocarcinoma with cTNM stage II/III，T≥3, N ≥0, M=0； 3. Expected survival of ≥ 3 months; 4. The tumor specimens were PD-L1 positive (CPS ≥ 1)； 5. There is a measurable lesion with the possibility of radical R0 resection after evaluation by doctors； 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 7. Patients informed about the purpose and course of the study and provided a written consent to participate.
Exclusion criteria
1. Use of taurine agent within 1 month prior to the first dose of study treatment and throughout the study; 2. Patients with positive HER-2； 3. Patients with gastrointestinal obstruction or active bleeding in the gastrointestinal tract, as well as perforation and dysphagia; 4. Patients with severe heart, lung, liver, kidney, endocrine, hematopoietic system or psychiatric diseases were considered not suitable for the study group; 5. Human immunodeficiency virus (HIV) infection or known acquired immune deficiency syndrome (AIDS) or autoimmune disease or immunosuppressant use； 6. There are patients who may increase the risk of participating in the study and study medication, or other severe, acute and chronic diseases, and are not suitable for participating in the clinical study according to the judgment of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response | Through study completion, Within 1 week after operation | To evaluate the pathologic complete response rate of locally advanced gastric cancer treated with concurrent serplulimab with chemotherapy with or without taurine supplementation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response (MPR) | Through study completion, Within 1 week after operation | Residual tumor cells below 10% in the resected specimen. |
| Objective response rate (ORR) | Through study completion, an average of 1 year. | ORR is defined as the proportion of subjects with complete response (CR) or partial response (PR) according to RECIST 1.1 criteria. |
| Disease-free survival (DFS) | Through study completion, an average of 1 year | 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. |
| Event-free survival (EFS) | Through study completion, an average of 1 year | 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. |
| R0 resection rate | Through study completion, Within 1 week after operation | The surgical margin is microscopically-negative for residual tumor. |
| Quality of life | Through study completion, an average of 1 year] | The quality of life was assessed by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-STO22 and Piper Fatigue Scale. |
| Changes in CD8+ T cell infiltration in tumor tissue | 1 year | 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. |
| Changes in CD8+ T cell death and function | Through study completion, an average of 1 year | 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. |
| Safety endpoints | Through study completion, an average of 1 year | 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. |
| Overall survival (OS) | Through study completion, an average of 1 year | 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. |
Countries
China
Contacts
Primary ContactXiaodi Zhao, MD, PhD
Backup ContactXin Wang, MD, PhD
Outcome results
None listed