Activity of Regorafenib in Combination With Chemotherapy in Patients With Advanced Biliary Tract Cancer

Inclusion Criteria: * Adenocarcinoma of the biliary tract * Metastatic disease with no curative surgery option or metastatic recurrence after resection. * Only for phase II: At least one measurable lesion in a non-irradiated area according to Response Evaluation Criteria in Solid Tumors * No biliary obstruction. * Age between 18 and 75 years. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy higher than 3 months. * No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy including Gemcitabine and/or platinum based is allowed if completed at least 6 months previously and relapsing after completion of the last dose. * Total bilirubin ≤ 2.5 times the upper limit of the normal range. Patients with jaundice or evidence of bile duct obstruction, in whom the biliary tree can be decompressed by endoscopic or percutaneous endoprothesis (at least 15 days before inclusion) with subsequent reduction in total bilirubin ≤ 3 ULN, will be eligible for the study. * Aminotransferases (AST, ALT) ≤ 2.5 ULN (≤ 5 ULN in case of diffuse hepatic involvement), INR \< 1.5 (following vitamin K1 injection in patients with current or recent history of jaundice or bile duct obstruction), serum creatinine clearance calculated \> 50 mL/min/1.73m² according to the Modification of Diet in Renal Disease (MDRD) formula, neutrophils ≥ 1.5.109/L, platelets ≥ 100.109/L, hemoglobin ≥ 9 g/dL (red blood cell transfusion is allowed if needed). * Signed infor…