Safety and Efficacy Study of Sorbitol with Neoadjuvant Chemotherapy Combined with Tirellizumab (PD-1 Inhibitor) in Patients with Locally Advanced Gastric Cancer

Phase 2

Recruiting

• Conditions: Gastric Junction Adenocarcinoma; Gastric Cancer; Immunotherapy; Neoadjuvant Therapies
• Interventions: Drug: Sorbitol; Other: Placebo

• Registration Number: NCT06826079
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

The goal of this clinical trial is to learn if sorbitol works to enhance the therapeutic effect of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. It will also learn about the safety of sorbitol. The main questions it aims to answer are:

Does sorbitol enhance the therapeutic effect of immunotherapy and increase the major response rate in patients with locally advanced gastric cancer? Does sorbitol with neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) can improve the prognosis of patients with locally advanced gastric cancer?

Researchers will compare sorbitol to a placebo (a look-alike substance that contains no drug) to see if sorbitol works to enhance the therapeutic effect of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. .

Participants will:

Take sorbitol or a placebo every day for 3 months in 3 treatment cycles Visit the clinic once every 4 weeks for checkups and tests Keep a diary of their symptoms and the number of times they use a rescue inhaler Participants will follow up as planned until PD occurs, informed consent is withdrawn, or follow-up is lost (whichever occurs first). After the end of treatment and safety follow-up, all subjects will be followed up for survival (OS data collected every 3 months ±14 days)..

Detailed Description

1. Overall Design This study is an exploratory investigation on the efficacy of oral sorbitol combined with SOX chemotherapy and tislelizumab (PD-1 inhibitor) in the neoadjuvant treatment of advanced gastric/gastroesophageal junction adenocarcinoma based on the concepts of tumor metabolism and immunity. The study is divided into three phases: screening period, treatment period (neoadjuvant treatment, surgery and adjuvant treatment period), and follow-up period. A total of 100 subjects will be enrolled in this study and randomly divided into two groups. Group A: oral sorbitol + PD1 inhibitor + SOX for 3 cycles (1 cycle = every 3 weeks \[Q3W\]); Group B: placebo + PD1 inhibitor + SOX for 3 cycles (1 cycle = every 3 weeks \[Q3W\]) (see below for details).

2. Screening Period:

Subjects must undergo screening and evaluation within 14 days before the first dose to determine their eligibility for the study. The specific criteria are: histologically confirmed, untreated HER2-negative gastric cancer or gastroesophageal junction (GEJ) cancer, with a clinical stage of cT3-4N+M0, and histological confirmation of mainly adenocarcinoma. Only Siewert type III and Siewert type II GEJ cancer patients who do not require combined thoracotomy are allowed to be enrolled. For patients who meet the inclusion and exclusion criteria, routine blood tests, imaging examinations, and Helicobacter pylori tests will be completed, and further molecular-level tests will be conducted, including MSI status, PD-1 expression CPS score, and EBER detection of pre-treatment biopsy pathological tissues.

The enrolled subjects will be randomly divided into two groups. Group A: oral sorbitol + PD1 inhibitor + SOX for 3 cycles (1 cycle = every 3 weeks \[Q3W\]); Group B: oral placebo + PD1 inhibitor + SOX for 3 cycles (1 cycle = every 3 weeks \[Q3W\]).

3. Treatment Period

The treatment period will include the following phases:

1. Neoadjuvant treatment (before surgery) period: 3 cycles Group A (sorbitol diet group): PD1 inhibitor + SOX for 3 cycles (1 cycle = every 3 weeks \[Q3W\]); During the neoadjuvant treatment period, oral sorbitol 2-4g per dose, three times a day (with meals).

Group B (placebo diet group): PD1 inhibitor + SOX for 3 cycles (1 cycle = every 3 weeks \[Q3W\]); During the neoadjuvant treatment period, oral placebo 2-4g per dose, three times a day (with meals).

2. Surgery: After evaluation of the efficacy of neoadjuvant treatment After neoadjuvant treatment, for subjects deemed eligible for surgery by the study, surgery should be performed within 2-6 weeks after the last dose of neoadjuvant treatment (including oral medication). For subjects who cannot undergo surgery, the subsequent treatment plan will be determined by the investigator based on the clinical situation. During the surgery, a small amount of pathological tissue should be taken and tested for AKR1B1/cGAS targets and sorbitol content.

3. Adjuvant treatment (after surgery) period: 5 cycles Adjuvant treatment stage: Unblinding after surgery, adjuvant treatment can start 3 weeks to 12 weeks after surgery (beyond 12 weeks, the investigator can decide whether to continue using the experimental drug). Subjects in Group A and Group B will be grouped according to TRG grading. Subjects with TRG scores of 0-1 will continue the original treatment plan, while those with TRG scores greater than 2 will only receive SOX chemotherapy for up to 5 cycles, or until the investigator determines that the subject has lost clinical benefit, died, is intolerant to toxicity, withdraws informed consent, or for other reasons specified in the protocol (whichever occurs first).

4. Follow-up Period: Including safety follow-up and survival follow-up. After the treatment ends, all subjects will be followed up. For subjects who discontinue treatment for reasons other than PD, follow-up will be conducted at the originally planned frequency until PD occurs, informed consent is withdrawn, or the subject is lost to follow-up (whichever occurs first). After the treatment ends and the safety follow-up is completed, all subjects will be followed up for survival (OS data will be collected every 3 months ± 14 days) until death, withdrawal of informed consent, loss to follow-up, or study termination (whichever occurs first).

Study Timeline

• Study Start: 2024-11-01
• Status Verified: 2025-02
• Study First Submitted: 2025-02-09
• Study First Submitted QC: 2025-02-09
• Study First Posted: 2025-02-13
• Last Update Submitted: 2025-02-16
• Last Update Posted: 2025-02-18
• Primary Completion: 2025-08-01
• Study Completion: 2028-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sorbitol	Sorbitol	-
placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
major pathological response	From enrollment to the end of treatment at 3 months
pathological complete response	From enrollment to the end of treatment at 3 months

Secondary Outcome Measures

Name	Time	Method
objective response rate	From enrollment to the end of treatment at 3 months
R0 resection rate	From enrollment to the end of treatment at 3 months

Trial Locations

Locations (1)

Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China