A randomized phase III trial comparing adjuvant chemotherapy with S-1 vs. surgery alone in patients with resectable biliary tract cancer (JCOG1202: ASCOT)

TPS4144 Background: No standard adjuvant treatment has been established for patients with curatively resected biliary tract cancer (BTC). S-1, which is one of the oral fluoropyrimidine derivatives, showed promising efficacy with a mild toxicity profiles in patients with advanced BTC, and the survival benefit of adjuvant S-1 therapy has been demonstrated in patients with resected gastric cancer and pancreatic cancer. The aim of this open-label, multicenter, randomized phase III trial is to assess whether adjuvant S-1 would prolong the overall survival in patients with resected BTC. Methods: The main eligibility criteria are as follows: 1) curatively resected carcinoma of the extrahepatic bile duct, gallbladder or ampulla of Vater (T2-4, N0, M0 or T1-4, N1, M0), or carcinoma of the intrahepatic bile duct (T1-4, N0-1, M0) (7th UICC classification), 2) histologically confirmed adeno (squamous) carcinoma, 3) R0 or R1 residual disease, 4) age 20 to 80 years, 5) ECOG performance status 0 or 1, 6) no prior chemotherapy or radiotherapy, 7) adequate organ functions, 8) written informed consent. Patients are randomly assigned to the surgery alone arm (arm A) or the adjuvant S-1 arm (arm B) by the minimization method for balancing institution, primary site of cancer and lymph node metastasis between the arms. Patients in arm A do not receive any anti-cancer treatment, while patients in arm B receive 4 cycles of oral S-1 chemotherapy at the dose of 40 mg/m2 twice daily for 4 weeks followed by 2 weeks of rest. The primary endpoint is overall survival, while the secondary endpoints are relapse-free survival, incidence of (serious) adverse events, and proportion of treatment completion. We assumed a 3-year survival in arm A of 47% and a 10% increase in the 3-year survival in arm B. The sample size was calculated as a total of 350, with a one-side alpha of 5% and power of 70%; planned accrual period is 4 years, and follow-up period, 3 years. Primary analysis will be conducted at 3 years and updated analysis will be conducted at 5 years after closing of accrual. As of Jan 31, 2016, a total of 285 patients have already been enrolled in this trial from Sep 2013. Clinical trial information: UMIN000011688.