Phase II study of chemoradiotherapy combined with gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic adenocarcinoma (NUPAT 05 trial)

Abstract

Background: For patients with metastatic pancreatic adenocarcinoma (PDAC), gemcitabine plus nab-paclitaxel (GnP) has shown improved survival and become one of the standard regimens worldwide. However, the efficacy of GnP for unresectable locally advanced (UR-LA) PDAC is still unclear, and also chemoradiotherapy for UR-LA PDAC is controversial. Therefore, we conducted phase I study of chemoradiotherapy using GnP to assess the toxicity and determined the recommended dose based on dose limited toxicity. From these results, we designed phase II trial to evaluate efficacy and toxicity of chemoratiotherapy combined with GnP for UR-LA PDAC. Method: Eligible requirements include chemotherapy-naïve patients diagnosed as UR-LA PDAC defined by NCCN guidelines. The patients will be administrated 100 mg/m2 nab-paclitaxel followed 800 mg/m2 gemcitabine on day 1, 8, 15, every 4 weeks. Radiation therapy is planned to deliver as a total dose of 50.4 Gy in 28 fractions, 1.8 Gy per day from day 1. Treatment will be continued until disease progression or surgery if the disease is well controlled. The estimated enrollment is 25 patients started recruiting from December 2017. The primary endpoint is 2-year overall survival rate. With two-sided alpha error of 0.05, this study is estimated to have 81.7% power to detect a 30% increase of the 2-year overall survival rate. Secondary endpoints are resection rate, OS, PFS, time to treatment failure, response rate, disease control rate, early tumor shrinkage, deepness of response, SUV-max on PET-CT, serum tumor markers, relative dose intensity, safety, and QoL. Clinical trials information: UMIN 000028116