Patients with locally advanced gastric cancer (LAGC), particularly those with serosal invasion, remain at high risk of peritoneal recurrence despite standard perioperative treatment. Hyperthermic intraperitoneal chemotherapy (HIPEC) may eradicate free intraperitoneal tumor cells and microscopic peritoneal disease while potentially enhancing systemic anti-tumor immune activation. This is a prospective, single-center, single-arm exploratory study evaluating a HIPEC priming strategy followed by serplulimab-based neoadjuvant therapy in patients with locally advanced gastric cancer (cT3-4aN+M0). Eligible patients will undergo diagnostic laparoscopy confirming no visible peritoneal metastasis (P0) and negative peritoneal cytology (CY0), followed by docetaxel-based HIPEC. After recovery from HIPEC, patients will initially receive one cycle of serplulimab combined with fluoropyrimidine monotherapy (S-1 or capecitabine), followed by subsequent cycles of serplulimab combined with SOX/XELOX chemotherapy prior to radical gastrectomy. The primary endpoints are pathological complete response (pCR) rate and major pathological response (MPR) rate. Secondary endpoints include R0 resection rate, objective response rate (ORR), peritoneal recurrence-free survival (PRFS), overall survival (OS), and safety.
Locally advanced gastric cancer (LAGC) remains associated with a high risk of recurrence after curative-intent treatment, particularly peritoneal recurrence in patients with serosal invasion. Although perioperative chemotherapy improves survival outcomes, current systemic treatment strategies remain insufficient for controlling microscopic peritoneal dissemination. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivers heated chemotherapeutic agents directly into the peritoneal cavity, resulting in enhanced regional drug exposure and hyperthermia-mediated cytotoxicity. In addition to direct anti-tumor effects, accumulating evidence suggests that HIPEC may induce immunogenic cell death, enhance tumor antigen release, and activate systemic anti-tumor immune responses. Serplulimab is a humanized anti-programmed cell death protein 1 (PD-1) monoclonal antibody that restores T-cell-mediated anti-tumor immunity through blockade of the PD-1/PD-L1 signaling pathway. The sequential administration of HIPEC followed by PD-1 blockade-based neoadjuvant therapy may therefore provide synergistic anti-tumor activity in locally advanced gastric cancer. This prospective, single-center, single-arm exploratory study is designed to evaluate the efficacy and safety of HIPEC followed by serplulimab-based neoadjuvant therapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma. Approximately 48 patients with clinically staged cT3-4aN+M0 disease will be enrolled. After screening and informed consent, all eligible patients will undergo diagnostic laparoscopy with peritoneal lavage cytology. Patients confirmed to have no visible peritoneal metastasis (P0) and negative cytology (CY0) will receive docetaxel-based HIPEC. Following postoperative recovery, patients will receive one induction cycle of serplulimab combined with fluoropyrimidine monotherapy (S-1 or capecitabine). Subsequent neoadjuvant treatment will consist of serplulimab combined with SOX or XELOX administered every 3 weeks for a total of 3-4 treatment cycles. Patients considered resectable after radiologic reassessment will undergo standard radical gastrectomy with D2 lymphadenectomy. The primary endpoints are pathological complete response (pCR) and major pathological response (MPR). Secondary endpoints include R0 resection rate, objective response rate (ORR), peritoneal recurrence-free survival (PRFS), overall survival (OS), and treatment-related safety assessed according to NCI-CTCAE criteria.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Docetaxel-based hyperthermic intraperitoneal chemotherapy administered after diagnostic laparoscopy in patients with P0/CY0 locally advanced gastric cancer
Serplulimab administered intravenously every 3 weeks as part of neoadjuvant treatment
Oral S-1 administered during neoadjuvant treatment.
Oral capecitabine administered during neoadjuvant treatment.
Intravenous oxaliplatin administered as part of SOX/XELOX neoadjuvant chemotherapy.
Standard radical gastrectomy with D2 lymphadenectomy performed after completion of neoadjuvant therapy.
Pathological Complete Response (pCR) Rate
Proportion of patients achieving pathological complete response, defined as the absence of residual viable tumor cells in both the primary tumor and regional lymph nodes after neoadjuvant treatment and radical gastrectomy.
Time frame: At the time of surgery
Major Pathological Response (MPR) Rate
Proportion of patients achieving major pathological response, defined as ≤10% residual viable tumor cells in the resected primary tumor specimen following neoadjuvant treatment.
Time frame: At the time of surgery
Objective Response Rate (ORR)
Proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST version 1.1.
Time frame: Perioperative
R0 Resection Rate
Proportion of patients achieving microscopically margin-negative (R0) resection.
Time frame: At surgery
Peritoneal Recurrence-Free Survival (PRFS)
Time from enrollment to the occurrence of peritoneal metastasis (peritoneal metastasis detected by PET/CT and/or diagnostic laparoscopy).
Time frame: Up to 3 years after surgery
Overall Survival (OS)
Time from study enrollment to death from any cause.
Time frame: Up to 3 years
Incidence of Treatment-Related Adverse Events
Incidence and severity of treatment-related adverse events assessed according to NCI-CTCAE version 6.0.
Time frame: From the date of informed consent signing until the end of the safety follow-up period (30 days after the last dose of study treatment)
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