SWOG S1505: A randomized phase II study of perioperative mFOLFIRINOX versus gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinoma.

Abstract

TPS547 Background: Clinical outcomes after curative therapy for resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. Series show that 70-85% of patients die of systemic recurrence. Improved overall survival (OS) in the metastatic setting with the use of multi-agent chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) holds the promise of progress in the curative setting as well. However, aggressive systemic therapy is usually not feasible after major pancreatic surgery. Therefore, early control of systemic disease by increased preoperative chemotherapy may improve outcomes. Furthermore, the perioperative platform facilitates early identification of patients with chemotherapy-resistant tumors and allows prospective biomarker studies in the future. Methods: This is a randomized phase II study intended to choose the most promising perioperative regimen to test in a larger trial. Eligibility requirements include adult patients with an ECOG PS of 0 or 1, a confirmed histopathologic diagnosis of PDA, and resectable disease as confirmed by central radiology review: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); no involvement, or < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Treatment includes 12 weeks [either 6 doses of mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin – without bolus 5-FU and leucovorin), or 9 doses of gemcitabine/nab-paclitaxel, on standard schedules] of preoperative chemotherapy, followed by surgical resection and 12 weeks of identical postoperative chemotherapy. Primary outcome is 2-year OS, using a “pick the winner” design with minimum two-year OS of 40% assuming a 58% alternative hypothesis, 88% power, and a 1-sided α of 0.05, providing 90% probability of selecting the better regimen with a total sample size of 150 patients. Correlative studies are planned. The study opened through the National Clinical Trials Network (NCT02562716), and is supported by NIH/NCI/NCTN grants CA180888, CA180819, CA180821, CA180833. Clinical trial information: NCT02562716.