Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1): A randomized, multidisciplinary, multinational phase III trial.

TPS4140 Background: Despite complete resection, disease free survival (DFS) and overall survival (OS) of patients with cholangiocarcinoma (CCA) or muscle invasive gallbladder carcinoma (GBCA) is poor. Thus, evaluation of adjuvant chemotherapy (CTx) in biliary tract cancer (BTC) in a large randomized trial is warranted. Methods: ACTICCA-1 is a phase III investigator initiated trial (EudraCT No 2012–005078-70). With respect to ABC-02 trial, cisplatin and gemcitabine for 24 weeks were selected as investigational treatment. Based on adjuvant trials in pancreatic cancer with a comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of CTx was chosen. Due to the different prognosis and treatment susceptibility of gallbladder carcinoma, two separate cohorts for CCA and GBCA were included. Randomization will be stratified for lymph node status for both cohorts and localization for CCA. The primary endpoint is DFS and secondary endpoints include OS, safety, tolerability and quality of life. For CCA, DFS 24 months post surgery (DFSR@24) is expected to be 40% without CTx. CTx should increase DFS@24 to 55% to be regarded as clinically relevant. With a power of 80% and a significance level of 5%, 271 evaluable study patients have to be followed for 24-28 months to observe 166 events. For GBCA, adjuvant CTx should increase DFSR@24 from 35% to 55% to be relevant; thus, 154 evaluable patients and 90 events are needed. In both cohorts, randomization will be 1:1 with adjuvant CTx for 24 weeks and imaging every 12 weeks. The ACTICCA-1 trial has been started in Germany (funded by the Deutsche Krebshilfe and supported by medac) in 2014 and recently in the Netherlands (funded by the Dutch Cancer Society and supported by medac). Furthermore, Australia, Denmark and the United Kingdom (funded by Cancer Research UK) will particpate within the next months. Conclusion: The randomized, multinational, multidisciplinary phase III ACTICCA-1 trial will establish the role of adjuvant gemcitabine and cisplatin in patients with BTC. Clinical trial information: NCT02170090.