A randomized, multi-center phase III trial of adjuvant chemotherapy with gemcitabine and capecitabine (GemCap) compared to capecitabine (Cap) alone in curatively resected biliary tract cancer (BilGemCap Study): KCSG HB20-14.

TPS633 Background: Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage; thus, only 20% of the patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. Recent phase 3 trials using single agent such as Cap or S1 support the role of adjuvant chemotherapy as standard of care in patients with resected BTCs, but the efficacy still needs to be further improved. Therefore, we designed a randomized, multi-center, phase 3 trial comparing GemCap with Cap in curatively resected BTC patients. Methods: The primary endpoint is 24-month disease-free survival (DFS) and secondary endpoints are overall survival (OS), quality of life (QOL), toxicities and exploratory biomarker analysis. Referring to the recent results of BILCAP study, the sample size calculation is based on the assumption that the 24-month DFS would be 50% in the Cap arm, and that treatment with GemCap would improve the 24-months DFS by 10%, from 50% to 60%. As such, 490 patients and 337 events are needed to detect a HR of 0.737, with a two-sided significance level of 5% and 80% power. Patients aged 19 years or older with macroscopically resected intra- or extrahepatic cholangiocarcinoma and muscle-invasive gallbladder cancer (T2-4 or N1-2, M0) are eligible. The Eastern Cooperative Oncology Group (ECOG) performance status have to be 0-1, and adequate renal, hematological, and liver function is required. Patients who had not completely recovered within 12 weeks from surgery or who had previous history of chemotherapy or radiotherapy for BTC are also excluded. Patients are randomly assigned 1:1 to the GemCap arm or the Cap arm, stratified by LN status (N0 vs. N+), resection status (R0 vs. R1) and primary site. After randomization, either oral Cap (1250 mg/m²) twice a day on days 1 to 14 of a 3-weekly cycle (8 cycles), or oral Cap (830 mg/m²) twice a day on days 1 to 21 plus Gem (830 mg/m²) on days 1, 8 and 15 of a 4-weeky cycle (6 cycles) are given. As of September 2022, 147 patents have been randomized to each arm, and updated study status will be presented. This is a collaborative study with Korean Cancer Study Group (KCSG) and Korean Pancreas Surgery Club (KPSC), supported by a grant from the National R&D Program for Cancer Control through the National Cancer Center (NCC) funded by the Ministry of Health & Welfare, Republic of Korea (HA22C0053). This is prospectively registered on ClinicalTrials.gov, NCT0005056. Clinical trial information: NCT0005056 .