Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is FDA-approved in USA for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. A phase 1/2 study in previously untreated locally advanced/metastatic PDAC showed promising anti-tumor activity with liposomal irinotecan 50mg/m free-base + 5-FU 2400mg/m + LV 400mg/m + oxaliplatin (OX) 60mg/m on days 1 and 15 of a 28-day cycle (Wainberg et al. Ann Oncol 2019;30 Suppl 4: SO-005). We present the phase-3 NAPOLI-3 study design, investigating the efficacy and safety of this regimen as first-line therapy in patients with mPDAC.
NAPOLI-3 (NCT04083235) is a phase-3, open-label, randomized, global study in adults with histologically/cytologically confirmed pancreatic adenocarcinoma, previously untreated in the metastatic setting. Patients must have ≥1 metastatic tumor measurable with computed tomography/magnetic resonance imaging and an Eastern Cooperative Oncology Group performance status score of 0–1. Site activation began in Dec-2019 and enrollment is ongoing. Random allocation (1:1) of 750 patients is planned to liposomal irinotecan + 5-FU/LV + OX (same regimen as phase 1/2 study) or nab-paclitaxel 125mg/m + gemcitabine 1000mg/m on days 1, 8 and 15 in a 28-day cycle. The primary endpoint is overall survival. Secondary endpoints (progression-free survival and overall response rate assessed with Response Evaluation Criteria in Solid Tumors v1.1) will be compared if primary endpoint shows superiority for liposomal irinotecan + 5-FU/LV + OX over nab-paclitaxel + gemcitabine. Safety assessments include adverse-event monitoring. Patients will continue treatment until disease progression, unacceptable toxicity or study withdrawal, and will then be followed for survival every 2-months until death or study-end (when all patients have died, withdrawn consent or lost to follow-up).
This study is funded by Ipsen.
© 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved.