Lanreotide for the prevention of postoperative pancreatic fistula (S2408): study protocol for a multicenter randomized controlled trial

Postoperative pancreatic fistula (POPF) remains the defining complication of pancreatectomy, leading to significant morbidity, mortality, and increased healthcare costs. Multiple studied interventions have failed to meaningfully reduce the incidence of POPF, which is estimated to affect 25–30% of distal pancreatectomy patients. Since the early 1990s, studies have explored the role of perioperative somatostatin analogs (SSAs) for POPF prophylaxis, including octreotide. A randomized trial of perioperative pasireotide reported a reduced incidence of POPF, but faced criticism due to its single-center design, inconvenient dosing regimen, and pasireotide’s high rate of dose-limiting side effects. Lanreotide is a more recently developed SSA with a simpler dosing regimen due to its depot formulation and a favorable side-effects profile that has been proposed for POPF prophylaxis. In a single-arm phase II trial, a single dose of preoperative lanreotide was associated with low POPF rates of 11% and 3% in patients undergoing pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), respectively. S2408 is a multicenter, phase III randomized controlled trial sponsored by the National Cancer Institute Division of Cancer Prevention comparing the incidence of POPF in participants receiving a single dose of preoperative lanreotide (120 mg subcutaneous) versus saline placebo immediately prior to DP for suspected or biopsy-proven pancreatic malignancy. Planned enrollment of 274 participants will take place at academic and community hospitals in North America. The primary objective is to compare the incidence of POPF within 60 days after surgery between treatment groups. Secondary objectives include comparing the incidences of other postoperative sequelae (biochemical leak, delayed gastric emptying, post-pancreatectomy hemorrhage) within 60 days of surgery, postoperative length of hospital stay, and changes from baseline in cancer-specific quality of life between treatment groups. Blood, drain fluid, and tissue specimens will be banked for future correlative studies. S2408 is a multicenter clinical trial designed to evaluate the hypothesis that a single dose of preoperative lanreotide will reduce the incidence of POPF in patients undergoing DP compared to placebo. ClinicalTrials.gov NCT06807437. Registered on February 2, 2025. Trial opened for accrual February 14, 2025. URL: https://clinicaltrials.gov/study/NCT06807437 .