Efficacy and Safety of Postoperative Concurrent Chemoradiotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma: A Multicenter Prospective Phase II Study

Summary

This is a multicenter, open-label, single-arm, prospective Phase II clinical trial. The study enrolls patients with extrahepatic cholangiocarcinoma or gallbladder carcinoma who have undergone curative resection and harbor high-risk recurrence factors, including: 1) narrow resection margin (including R1 resection); 2) positive circumferential resection margin; 3) T stage ≥ T3-4; 4）positive regional lymph nodes. All patients will receive postoperative concurrent chemoradiotherapy (CCRT) with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). The high-risk volumes of the primary tumor bed and metastatic lymph node beds will be irradiated to 48-60 Gy in 20-25 fractions. Retroperitoneal and intra-abdominal lymph nodes will receive 50-57.5 Gy in 20-25 fractions, and lymphatic drainage regions will be treated to 40-45 Gy in 20-25 fractions. During radiotherapy, concurrent oral capecitabine will be administered at a dose of 1,600 mg/m² on Days 1-14, every 21 days for 2 cycles. Following the completion of radiotherapy, maintenance oral capecitabine will be continued at 2,000 mg/m² on Days 1-14, every 21 days for 6 cycles. For patients intolerant to capecitabine, S-1 will be substituted: concurrent S-1 40-50 mg twice daily on Days 1-28, every 42 days for 1 cycle, followed by maintenance S-1 40-60 mg twice daily on Days 1-28, every 42 days for 3 cycles. The primary study endpoint is the 2-year recurrence-free survival (RFS) rate. Secondary study endpoints include the 2-year overall survival (OS) rate, locoregional control rate, and incidence of grade ≥3 adverse events. A total of 92 patients are planned for enrollment in this trial.

Timeline

Start

2026-06-16

Primary completion

2029-02-28

Completion

2029-05-30

Publications

• Background Zheng Q, Lv B, Chen Y, Hsu S, Zhang Y, Wang S, Liu H, Suo T, Zeng Z, Du S. Adjuvant Chemoradiation Therapy Versus Chemotherapy Alone After Resection of Gallbladder Carcinoma: A Real-World, Inverse Probability of Treatment Weighting-Based Cohort Study. Int J Radiat Oncol Biol Phys. 2026 Feb 1;124(2):415-427. doi: 10.1016/j.ijrobp.2025.09.023. Epub 2025 Sep 16.
• Background Gholami S, Colby S, Horowitz DP, Guthrie KA, Ben-Josef E, El-Khoueiry AB, Blanke CD, Philip PA, Kachnic LA, Ahmad SA, Rocha FG. Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809). Ann Surg Oncol. 2023 Mar;30(3):1354-1363. doi: 10.1245/s10434-022-12863-9. Epub 2023 Jan 9.
• Background Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, Thomas CR Jr, Alberts SR, Dawson LA, Micetich KC, Thomas MB, Siegel AB, Blanke CD. SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma. J Clin Oncol. 2015 Aug 20;33(24):2617-22. doi: 10.1200/JCO.2014.60.2219. Epub 2015 May 11.
• Background Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012 Jun 1;30(16):1934-40. doi: 10.1200/JCO.2011.40.5381. Epub 2012 Apr 23.
• Background Kamarajah SK, Bednar F, Cho CS, Nathan H. Survival benefit with adjuvant radiotherapy after resection of distal cholangiocarcinoma: A propensity-matched National Cancer Database analysis. Cancer. 2021 Apr 15;127(8):1266-1274. doi: 10.1002/cncr.33356. Epub 2020 Dec 15.
• Background Ren B, Guo Q, Yang Y, Liu L, Wei S, Chen W, Tian Y. A meta-analysis of the efficacy of postoperative adjuvant radiotherapy versus no radiotherapy for extrahepatic cholangiocarcinoma and gallbladder carcinoma. Radiat Oncol. 2020 Jan 15;15(1):15. doi: 10.1186/s13014-020-1459-x.
• Background Jeong H, Kim KP, Jeong JH, Hwang DW, Lee JH, Kim KH, Moon DB, Lee MA, Park SJ, Chon HJ, Park JH, Lee JS, Ryoo BY, Yoo C. Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial. Hepatology. 2023 May 1;77(5):1540-1549. doi: 10.1097/HEP.0000000000000046. Epub 2023 Jan 3.
• Background Nakachi K, Ikeda M, Konishi M, Nomura S, Katayama H, Kataoka T, Todaka A, Yanagimoto H, Morinaga S, Kobayashi S, Shimada K, Takahashi Y, Nakagohri T, Gotoh K, Kamata K, Shimizu Y, Ueno M, Ishii H, Okusaka T, Furuse J; Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG). Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2023 Jan 21;401(10372):195-203. doi: 10.1016/S0140-6736(22)02038-4.
• Background Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J; BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019 May;20(5):663-673. doi: 10.1016/S1470-2045(18)30915-X. Epub 2019 Mar 25.
• Background Tran Cao HS, Zhang Q, Sada YH, Chai C, Curley SA, Massarweh NN. The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts. Cancer. 2018 Jan 1;124(1):74-83. doi: 10.1002/cncr.30968. Epub 2017 Aug 25.
• Background Wheless M, Agarwal R, Goff L, Lockney N, Padmanabhan C, Heumann T. Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma. Curr Treat Options Oncol. 2024 Jan;25(1):127-160. doi: 10.1007/s11864-023-01153-5. Epub 2024 Jan 5.
• Background Bridgewater JA, Goodman KA, Kalyan A, Mulcahy MF. Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling. Am Soc Clin Oncol Educ Book. 2016;35:e194-203. doi: 10.1200/EDBK_160831.
• Background Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D; ESMO Guidelines Committee. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v28-v37. doi: 10.1093/annonc/mdw324. No abstract available.
• Background Saha SK, Zhu AX, Fuchs CS, Brooks GA. Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise. Oncologist. 2016 May;21(5):594-9. doi: 10.1634/theoncologist.2015-0446. Epub 2016 Mar 21.
• Background Mirallas O, Lopez-Valbuena D, Garcia-Illescas D, Fabregat-Franco C, Verdaguer H, Tabernero J, Macarulla T. Advances in the systemic treatment of therapeutic approaches in biliary tract cancer. ESMO Open. 2022 Jun;7(3):100503. doi: 10.1016/j.esmoop.2022.100503. Epub 2022 Jun 10.

Drugs

Indications