Randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan Clinical Oncology Group Study (JCOG1407)

Abstract

Background: Gemcitabine (GEM) is a standard treatment for locally advanced pancreatic cancer (LAPC), but the prognosis is still poor. FOLFIRINOX and GEM plus nabpaclitaxel (GnP) have recently shown superior efficacy over GEM in patients (pts) with metastatic disease, and may also benefit LAPC pts. In addition, phase II study of modified FOLFIRINOX (mFOLFIRINOX), in which dose of irinotecan was reduced and bolus 5‐FU was omitted, conducted in Japan showed comparable efficacy with original regimen and tolerable toxicity. The aim of this study is to evaluate the efficacy and safety of mFOLFIRINOX and GnP to determine which is more promising regimen for LAPC. Another aim of this study is to compare the selected regimen with historical control of GEM to determine which should be a standard therapy for LAPC. Trial design: Chemotherapy‐naïve pts with LAPC, an ECOG PS of 0‐1, aged 20‐75, and adequate organ function are randomized to mFOLFIRINOX orGnP. In the mFOLFIRINOX arm, 85 mg/m2 of oxaliplatin, 200mg/m2 of l‐leucovorin, 150mg/m2 of irinotecan, followed by 2,400mg/m2 of continuous 5‐FU over 46 hours are infused every 2weeks. In theGnP arm, 125mg/m2 of nab‐paclitaxel followed by 1,000mg/m2 of gemcitabine are infused on days 1, 8, and 15 every 4 weeks. Both treatments are continued until disease progression or unacceptable toxicity. The primary endpoint is 1‐year overall survival (OS). To select the more effective regimen in 1‐yearOS (53% vs ≥63%), 106 pts are needed with a probability of at least 0.85. After selecting the more promising regimen, to judge that regimen replaces GEMas a standard chemotherapy for LAPC, 120 pts are needed tomaintain 80% power under the hypothesis of 1‐year OS as the expected value of 70% and threshold value of 53% with one‐sided alpha of 5%. The planned total sample size is 124 pts considering for a few ineligible pts and lost to follow‐up. The planned accrual period is 2.5 years, and the follow‐up period is 1 year for primary analysis. Thirty‐six institutions are participating in this study.