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

Обзор

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.

Вмешательства

• Лучевая терапия Postoperative radiotherapy
  All patients will receive postoperative concurrent chemoradiotherapy with IMRT or 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.
• Препарат Capecitabine or S-1
  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

Первичные конечные точки

• 2-year recurrence-free survival (RFS) rate [Срок оценки: From completion of radiotherapy until 2 years after radiotherapy]

Вторичные конечные точки (3)

• 2-year overall survival (OS) rate [Срок оценки: From completion of radiotherapy until 2 years after radiotherapy]
• Locoregional control rate [Срок оценки: From completion of radiotherapy until 2 years after radiotherapy]
• Incidence of grade ≥3 treatment-related adverse events [Срок оценки: From initiation of radiotherapy until 3 months after radiotherapy]

Критерии участия

Критерии включения

• Aged 18-80 years
• Underwent curative resection for newly diagnosed disease, with postoperative pathology confirming extrahepatic cholangiocarcinoma or gallbladder adenocarcinoma
• Postoperative pathology with ≥1 high-risk factor for recurrence

• Narrow resection margin (<1 cm), including R1 resection
• Positive circumferential resection margin
• T stage ≥ T3-4
• Positive regional lymph nodes
• Postoperative liver function: Child-Pugh grade A5-B7
• No recurrence or metastasis before postoperative radiotherapy
• ECOG performance status 0-2
• Expected survival >3 months
• Routine blood tests: Neutrophils ≥1.0×10⁹/L, hemoglobin ≥80 g/L, platelets ≥100×10⁹/L
• Liver function: Total bilirubin <1.5×upper limit of normal (ULN), plus one of the following:

• ALT and AST ≤2.5×ULN
• ALT ≤1.5×ULN and AST ≤6×ULN (excluding AST elevation due to myocardial infarction)
• Renal function: Creatinine and blood urea nitrogen ≤2.5×ULN
• Voluntary participation and signed informed consent

Критерии исключения

• History of other malignant tumors (except papillary thyroid carcinoma, basal cell carcinoma of the skin, and cervical carcinoma in situ)
• Severe comorbidities (e.g., myocardial infarction, arrhythmia, psychiatric disorders)
• Prior abdominal radiotherapy
• Post-organ transplantation
• Symptomatic moderate-severe ascites within 4 months postoperatively
• ≥4 months since surgery

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences — Пекин

Публикации

• 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. PMID 40967375
• 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. PMID 36622529
• 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: PMID 25964250
• 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. PMID 22529261
• 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. PMID 33320344
• 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. PMID 31941520
• 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. PMID 37070950
• 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, ASCO PMID 36681415

Идентификаторы

NCT: NCT07636824 · NCC6244

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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