A multicenter randomized phase II study of UFT/leucovorin and radiotherapy (RT) with or without cetuximab following induction gemcitabine plus capecitabine (GEM-CAP) in locally advanced pancreatic cancer (LAPC).

Abstract

TPS221 Background: The optimal treatment paradigm for patients (pts) with LAPC has not yet been defined. Pooled analysis of GERCOR phase II-III studies suggests that pts may benefit from chemoradiotherapy (CRT) after achieving disease stabilization from induction chemotherapy (Huguet et al, JCO 2007). GEM-CAP resulted in a significant improvement in response rate and progression-free survival over gemcitabine in pts with LAPC (Cunningham et al, JCO 2009). UFT is well tolerated as a radiosensitizer in LAPC, and results in a R0 resection rate of 17% (J Bjerregaard et al, Radiother Oncol 2009). Cetuximab is an effective radiosensitiser in pts with squamous cell carcinoma of the head and neck (J Bonner et al, NEJM 2006), and its role as a radiosensitizer in other epithelial malignancies warrants further investigation. This randomized study aims to assess the overall survival (OS) for pts with LAPC receiving UFT/LV and radiotherapy with or without cetuximab after receiving induction GEM-CAP. Methods: Pts eligible for this study must have unresectable, histology-proven LAPC. Unresectability is based on extensive peri-pancreatic lymph node involvement; encasement/occlusion of superior mesenteric vein (SMV) or SMV/portal vein confluence ± involvement of superior mesenteric artery, coeliac axis, inferior vena cava, or aorta. Pts receive 3 cycles of neoadjuvant GEM-CAP. Those with disease stabilization or response receive one further cycle of GEM-CAP and proceed to RT (54Gy in 30# over 6 weeks) plus concurrent UFT with randomization to cetuximab. Functional imaging with diffusion weighted MRI and PET will be performed at baseline, weeks 4 and 16 to assess early predictors for efficacy. Pharmacogenetic studies with patients' germline DNA and correlative biomarker studies with pretreatment pancreatic biopsy will be performed. The primary endpoint is 1-yr OS rate. Using Simon one stage design, 1-yr OS rate from the time of registration of ≥55% is considered acceptable (p1) and <35% would be unacceptable (p0). 45 pts per arm will be randomized (2-sided α=0.05, 80% power). The trial opened in December 2009. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, Roche Roche Merck