Efficacy of neoadjuvant FOLFIRINOX in resectable pancreatic cancer (NeoFOL-R): study protocol for an international, multicenter, prospective, randomized controlled trial

Background: Recent randomized controlled trials (RCTs) regarding the outcomes of neoadjuvant chemotherapy for patients with resectable pancreatic cancer (PC) reported inconsistent results. As the survival rate of FOLFIRINOX was found to be superior to that of gemcitabine, interest in the efficacy of neoadjuvant chemotherapy with FOLFIRINOX for resectable PC is growing. In this study, we aimed to investigate the efficacy of neoadjuvant FOLFIRINOX in patients with resectable PC. Methods: This international (South Korea, Australia, and Taiwan), multicenter, phase 3, RCT will include 609 patients with resectable pancreatic ductal adenocarcinoma and ECOG performance 0–1. Resectable PC is defined as no arterial contact and no tumour contact with the superior mesenteric vein/portal vein or ≤ 180°contact without vein contour irregularity. Neoadjuvant FOLFIRINOX consisted of oxaliplatin (85 mg/m²), administered intravenously over 2 h, followed by leucovorin (400 mg/m²) over 2 h and irinotecan (180 mg/m²) over 90 min, administered concurrently. Subsequently, an intravenous bolus infusion of 5-FU (400 mg/m²) and a continuous infusion of 5-FU (2400 mg/m²) over 46 h, repeated every 2 weeks for 6 cycles. Adjuvant therapy with modified FOLFIRINOX (mFOLFIRINOX) included oxaliplatin (85 mg/m²), irinotecan (150 mg/m²), leucovorin (400 mg/m²), and fluorouracil (2400 mg/m²) over 46 h and repeated every 2 weeks, with six cycles in the neoadjuvant group and 12 cycles in the upfront surgery group. The primary endpoint is a two-year survival rate by intention-to-treat. Secondary outcomes are overall survival, disease-free survival, resection rate, R0 resection rate, lymph node negative rate, recurrence rate, response rate. When calculating with a significance level of 5% and a statistical power of 80%, 171 events (deaths) are needed. Considering the 5-year participant enrollment period and a minimum of a 2-year follow-up period, 518 patients were required to observe 171 events. A total of 609 patients were required when the dropout rate was calculated as 15%. Discussion: The NeoFOL-R trial investigates the efficacy of perioperative versus adjuvant FOLFIRINOX for patients with resectable PC. The study is ongoing, starting in February 2024 in South Korea, Australia, and Taiwan. Trial registration: NCT 05529940. Registered in September 2022. KCT0008360 (Korean Clinical Trial Database). Registered in April 2022.