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

Abstract

BackgroundDespite complete resection, disease-free survival (DFS) of patients with cholangiocarcinoma (CCA) is less than 65 % after one year and not more than 35 % after three years. For muscle invasive gallbladder carcinoma (GBCA), prognosis is even worse, with an overall survival (OS) of only 30 % after three years. Thus, evaluation of adjuvant chemotherapy in biliary tract cancer in a large randomized trial is warranted.Methods/DesignACTICCA-1 is a randomized, multidisciplinary, multinational phase III investigator initiated trial. With respect to data obtained in the ABC-02 trial, we selected the combination of gemcitabine and cisplatin for 24 weeks as investigational treatment. Based on adjuvant trials in pancreatic cancer with comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of chemotherapy was stipulated. Due to the different prognosis and treatment susceptibility of muscle invasive carcinoma, two separate cohorts (CCA and GBCA) were included to capture the potentially different treatment effects. Randomization is stratified for lymph node status for both cohorts and localization for CCA. The primary endpoint is DFS and secondary endpoints include OS, safety and tolerability of chemotherapy, quality of life, and patterns of disease recurrence. For CCA, adjuvant chemotherapy should increase DFS 24 months post-surgery from 40 to 55 % to be considered 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, chemotherapy should increase DFS 24 months post-surgery from 35 to 55 % to be of relevance; thus, 154 evaluable study patients have to be monitored for 24–28 months to observe 90 events. In both cohorts, randomization will be 1:1 with chemotherapy for 24 weeks and imaging every twelve weeks. In 2014, the study was initiated in Germany and in The Netherlands (funded by the Deutsche Krebshilfe, the Dutch Cancer Society, and supported by medac GmbH). Sites in Australia, Denmark, and the United Kingdom (funded by Cancer Research UK) are joining 2015.Trial registrationThe study is registered with ClinicalTrials.gov (NCT02170090) and the European Clinical Trials Database (2012-005078-70). Registration date is 06/18/2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1498-0) contains supplementary material, which is available to authorized users.

Surgical management of recurrent intrahepatic cholangiocarcinoma: predictors, adjuvant chemotherapy, and surgical therapy for recurrence: A multi‐institutional study by the Kyushu Study Group of Liver Surgery

“…did not mention the details of the adjuvant chemotherapy regimen and, also, our findings are based on various chemotherapy regimens. A randomized, multidisciplinary, multinational phase III trial concerning adjuvant chemotherapy with gemcitabine and cisplatin in patients with cholangiocarcinoma (the ACTICCA‐1 trial) is ongoing,23 and the results of the ACTICCA‐1 trial will be important information regarding the clinical efficacy of adjuvant chemotherapy in patients with ICC.…”

Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases

“…This is contrary to phase III trials that support palliative chemotherapy more than adjuvant chemotherapy. (24, 25)…”

The role of surgery and adjuvant therapy in lymph node–positive cancers of the gallbladder and intrahepatic bile ducts

“…Furthermore, the generalizability of results from the only previous phase 3 trial evaluating adjuvant therapy for BTCs is unclear because of the high rate of margin‐positive resection (R+) and because the chemotherapy regimen and schedule evaluated in this study are uncommonly used in contemporary practice . Additional prospective, randomized trials of adjuvant therapy for localized BTCs are either ongoing or have recently finished accrual …”