Work

Efficacy and safety of HIPEC combined with PD-1 and SOX chemotherapy for gastric or oesophagogastric junctional cancer with peritoneal metastasis (HISTORIA): protocol for a prospective, multicentre, single-arm, phase II study

Year: 2025

Type: article

Abstract: Introduction Despite advances in diagnostics, many patients with gastric cancer (GC) or oesophagogastric junction cancer present with advanced disease, most commonly peritoneal metastasis (PM), which conveys a poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and anti-programmed cell death protein-1 (PD-1) therapy have each shown promise in GC. We describe the protocol for a study evaluating the efficacy and safety of combining HIPEC with the anti-PD-1 antibody tislelizumab and SOX (oxaliplatin+S-1) chemotherapy in patients with GC/oesophagogastric junction cancer and PM. Methods and analysis This is a multicentre, single-arm, phase II trial conducted at 13 high-volume tertiary referral hospitals across China. We will enrol 50 adults (18–75 years) with histologically confirmed GC/oesophagogastric junction adenocarcinoma and PM diagnosed by laparoscopy. Participants will receive one laparoscopy-guided HIPEC cycle (paclitaxel, total dose: 175 mg/m2, 3000 mL of physiological saline at 43°C for 60 min, inflow rate 1.5 L/min, 10 min physiological saline preconditioning at 41°C) followed—after a 3-week interval—by up to three 3-week cycles of tislelizumab 200 mg plus SOX (oxaliplatin 130 mg/m² and S-1 dose-escalated by body surface area). HER2-positive patients will also receive trastuzumab. Primary endpoint: 1-year overall survival. Secondary endpoints: 1-year progression-free survival, completeness of Cytoreduction Score and objective response rate. Follow-up includes imaging and toxicity assessments every 3 months for at least 1 year. Ethics and dissemination The protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (ID 2024-SR-198). All participants will provide written informed consent. Results will be disseminated via peer-reviewed publications; de-identified individual participant data will be available from the corresponding author on reasonable request after publication. Trial registration number ClinicalTrials.gov, NCT06427252

Source: BMJ Open

DOI: 10.1136/bmjopen-2024-098326