Gemcitabine (GEM) is a standard treatment for locally advanced pancreatic cancer (LAPC), but the prognosis is still poor. FOLFIRINOX and GEM plus nab-paclitaxel (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.
Chemotherapy-naïve pts with LAPC, an ECOG PS of 0–1, aged 20-75, and adequate organ function are randomized to mFOLFIRINOX or GnP. In the mFOLFIRINOX arm, 85 mg/m2 of oxaliplatin, 200 mg/m2 of l-leucovorin, 150 mg/m2 of irinotecan, followed by 2,400 mg/m2 of continuous 5-FU over 46 hours are infused every 2 weeks. In the GnP arm, 125 mg/m2 of nab-paclitaxel followed by 1,000 mg/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-year OS (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 GEM as a standard chemotherapy for LAPC, 120 pts are needed to maintain 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. This study was activated in July 2016 and 24 pts were enrolled as of Apr 30, 2017.
Clinical trial identification
Legal entity responsible for the study
Japan Clinical Oncology Group
MHLW, Japan and Japan AMED
A. Fukutomi: Honoraria from Taiho Pharmaceutical, Lilly Japan, Yakult Honsha and Daiichi Sankyo. Advisory Role from Yakult Honsha. Research Funding from Taiho Pharmaceutical. T. Okusaka: Honoraria from Taiho Pharmaceutical, Lilly Japan and Yakult Honsha. Advisory Role from Lilly Japan, Taiho Pharmaceutical and Daiichi Sankyo. Research Funding from Lilly, Yakult Honsha and Taiho Pharmaceutical. N. Okano: Research Funding from Taiho Pharmaceutical, Lilly Japan, Yakult and Daiichi Sankyo. N. Mizuno: Honoraria from Taiho Pharmaceutical, Lilly and Yakult Honsha. Speakers\' Bureau from Taiho Pharmaceutical. Travel Expenses from Taiho Pharmaceutical and Yakult Honsha. Research Funding from Taiho Pharmaceutical. M. Ikeda: Honoraria from Taiho Pharmaceutical, Lilly Japan and Daiichi Sankyo. Advisory Role from Lilly Japan. Research Funding from Taiho Pharmaceutical, Yakult and Lilly Japan. M. Ueno: Honoraria from Taiho Pharmaceutical, Yakult Honsha and Lilly. Research Funding from Taiho Pharmaceutical and Daiichi Sankyo. M. Ozaka: Honoraria from Taiho Pharmaceutical and Yakult Honsha. S. Shimizu, H. Fukuda: Honoraria from Taiho Pharmaceutical. S. Kondo: Research Funding from Lilly. H. Ishii: Honoraria from Yakult Honsha, Taiho Pharmaceutical and Lilly Japan. Research Funding from Taiho Pharmaceutical. J. Furuse: Honoraria and Research Funding from Taiho Pharmaceutical, Yakult, Lilly Japan and Daiichi Sankyo. Advisory Role and Speakers\' Bureau from Taiho Pharmaceutical and Yakult. Advisory Role from Lilly Japan. All other authors have declared no conflicts of interest.