Application of Intraperitoneal Hyperthermic Chemotherapy in the Treatment of Gastric Cancer With Peritoneal Metastasis

This clinical study is designed to evaluate a combined treatment approach in adults with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that has spread to the peritoneum (peritoneal metastasis), as confirmed by imaging, peritoneal fluid analysis, or laparoscopy. The study population also includes patients with malignant ascites. These patients have experienced disease progression despite receiving standard therapy. Management of this condition is particularly challenging because systemically administered chemotherapeutic agents achieve limited concentrations at peritoneal tumor sites, resulting in suboptimal disease control. In this study, participants will receive a multi-modal treatment regimen consisting of the following components administered concurrently: (1) heated intraperitoneal chemotherapy (HIPEC) using nab-paclitaxel (albumin-bound paclitaxel), delivered directly into the abdominal cavity via a device that maintains the perfusate temperature at 42-43°C; (2) retlirafusp alfa, a PD-L1/TGF-βRII bispecific antibody fusion protein that simultaneously blocks two signaling pathways involved in tumor proliferation and angiogenesis; (3) intravenous nab-paclitaxel; and (4) apatinib, an oral small-molecule VEGFR-2 inhibitor that suppresses tumor-driven angiogenesis. The hyperthermia is expected to enhance the cytotoxic efficacy of intraperitoneal chemotherapy against peritoneal tumor deposits, while the bispecific antibody and apatinib are intended to control extra-peritoneal disease. The primary objective of this study is to assess the safety and efficacy of this combined regimen, with a focus on disease control and overall survival. Participants will first complete an induction treatment phase, followed by repeated treatment cycles administered approximately every three weeks, and then proceed to maintenance therapy with retlirafusp alfa alone for up to two years. Throughout the study, participants will undergo regular imaging scans, laboratory tests, and clinical evaluations to monitor tumor response, treatment-related adverse events, and quality of life. This is a single-center study conducted in China.

Inclusion Criteria: Histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma Pathologically confirmed peritoneal metastasis, including positive cytology or tissue biopsy Advanced gastric or gastroesophageal junction adenocarcinoma that has progressed after standard therapy Age ≥ 18 years; Eastern Cooperative Oncology Group performance status score of 0 to 1; life expectancy ≥ 3 months Adequate cardiac, hepatic, renal, and bone marrow function, with ability to tolerate systemic anticancer therapy Willingness to participate in the study and provide written informed consent Exclusion Criteria: Gastric perforation or intestinal obstruction requiring gastrointestinal decompression; uncontrolled massive pleural effusion or ascites; or active bleeding History of hypersensitivity to paclitaxel-class drugs Severe cardiovascular or cerebrovascular disease; severe hepatic or renal impairment; active infection; coagulation disorder; history of immunodeficiency or current immunosuppressive therapy; uncontrolled epilepsy or central nervous system disease Pregnancy or lactation; any severe comorbidity or psychiatric disorder that, in the investigator's judgment, makes the participant unsuitable for study participation