Neoadjuvant HAIC of TACE Plus Donafenib in BCLC B Stage HCC: a Multi-center Randomized Controlled Trial.

Summary

The purpose of this study is to evaluate the safety and efficacy of the combination therapy with HAIC-TACE and donafenib compared to TACE plus donafenib in patients with BCLC B stage unresectable hepatocellular carcinoma (HCC) out of up-to-seven criteria.

Timeline

Start

2021-12-24

Primary completion

2025-10-31

Completion

2025-10-31

Publications

• Background Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3.
• Background Farsad K, Nabavizadeh N, Kardosh A, Jou JH, Naugler WE, Kolbeck KJ. Combined locoregional and systemic therapy for advanced hepatocellular carcinoma: finally, the future is obscure. Ann Transl Med. 2020 Dec;8(24):1700. doi: 10.21037/atm-20-4164. No abstract available.
• Background Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018 Mar 31;391(10127):1301-1314. doi: 10.1016/S0140-6736(18)30010-2. Epub 2018 Jan 5.
• Background Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.
• Background Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429-42. doi: 10.1053/jhep.2003.50047.
• Background Kokudo N, Takemura N, Hasegawa K, Takayama T, Kubo S, Shimada M, Nagano H, Hatano E, Izumi N, Kaneko S, Kudo M, Iijima H, Genda T, Tateishi R, Torimura T, Igaki H, Kobayashi S, Sakurai H, Murakami T, Watadani T, Matsuyama Y. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update. Hepatol Res. 2019 Oct;49(10):1109-1113. doi: 10.1111/hepr.13411. Epub 2019 Sep 6.
• Background European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019. Epub 2018 Apr 5. No abstract available.
• Background Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-380. doi: 10.1002/hep.29086. No abstract available.
• Background Wang Q, Xia D, Bai W, Wang E, Sun J, Huang M, Mu W, Yin G, Li H, Zhao H, Li J, Zhang C, Zhu X, Wu J, Li J, Gong W, Li Z, Lin Z, Pan X, Shi H, Shao G, Liu J, Yang S, Zheng Y, Xu J, Song J, Wang W, Wang Z, Zhang Y, Ding R, Zhang H, Yu H, Zheng L, Gu W, You N, Wang G, Zhang S, Feng L, Liu L, Zhang P, Li X, Chen J, Xu T, Zhou W, Zeng H, Zhang Y, Huang W, Jiang W, Zhang W, Shao W, Li L, Niu J, Yuan J, Li X, Lv Y, Li K, Yin Z, Xia J, Fan D, Han G; China HCC-TACE Study Group. Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study. J Hepatol. 2019 May;70(5):893-903. doi: 10.1016/j.jhep.2019.01.013. Epub 2019 Jan 18.
• Background Wang Q, Xia D, Bai W, Wang E, Han G. Reply to: "The "six-and-twelve score" for TACE treatment: Does it really help us?". J Hepatol. 2019 Nov;71(5):1053-1054. doi: 10.1016/j.jhep.2019.07.009. Epub 2019 Sep 26. No abstract available.
• Background Arizumi T, Minami T, Chishina H, Kono M, Takita M, Yada N, Hagiwara S, Minami Y, Ida H, Ueshima K, Kamata K, Minaga K, Komeda Y, Takenaka M, Sakurai T, Watanabe T, Nishida N, Kudo M. Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2. Dig Dis. 2017;35(6):589-597. doi: 10.1159/000480208. Epub 2017 Oct 17.
• Background Tsurusaki M, Murakami T. Surgical and Locoregional Therapy of HCC: TACE. Liver Cancer. 2015 Sep;4(3):165-75. doi: 10.1159/000367739. Epub 2015 Jul 10.
• Background Golfieri R, Giampalma E, Renzulli M, Cioni R, Bargellini I, Bartolozzi C, Breatta AD, Gandini G, Nani R, Gasparini D, Cucchetti A, Bolondi L, Trevisani F; PRECISION ITALIA STUDY GROUP. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014 Jul 15;111(2):255-64. doi: 10.1038/bjc.2014.199. Epub 2014 Jun 17.
• Background Sacco R, Bargellini I, Bertini M, Bozzi E, Romano A, Petruzzi P, Tumino E, Ginanni B, Federici G, Cioni R, Metrangolo S, Bertoni M, Bresci G, Parisi G, Altomare E, Capria A, Bartolozzi C. Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2011 Nov;22(11):1545-52. doi: 10.1016/j.jvir.2011.07.002. Epub 2011 Aug 16.
• Background Angelico M. TACE vs DEB-TACE: Who wins? Dig Liver Dis. 2016 Jul;48(7):796-7. doi: 10.1016/j.dld.2016.05.009. Epub 2016 May 17. No abstract available.
• Background Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.
• Background Kudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H, Izumi N, Yamasaki T, Nojiri S, Hino K, Tsumura H, Kuzuya T, Isoda N, Yasui K, Aino H, Ido A, Kawabe N, Nakao K, Wada Y, Yokosuka O, Yoshimura K, Okusaka T, Furuse J, Kokudo N, Okita K, Johnson PJ, Arai Y; TACTICS study group. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020 Aug;69(8):1492-1501. doi: 10.1136/gutjnl-2019-318934. Epub 2019 Dec 4.
• Background Qu XD, Chen CS, Wang JH, Yan ZP, Chen JM, Gong GQ, Liu QX, Luo JJ, Liu LX, Liu R, Qian S. The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma. BMC Cancer. 2012 Jun 21;12:263. doi: 10.1186/1471-2407-12-263.
• Background Wan X, Zhai X, Yan Z, Yang P, Li J, Wu D, Wang K, Xia Y, Shen F. Retrospective analysis of transarterial chemoembolization and sorafenib in Chinese patients with unresectable and recurrent hepatocellular carcinoma. Oncotarget. 2016 Dec 13;7(50):83806-83816. doi: 10.18632/oncotarget.11514.
• Background Yao X, Yan D, Zeng H, Liu D, Li H. Concurrent sorafenib therapy extends the interval to subsequent TACE for patients with unresectable hepatocellular carcinoma. J Surg Oncol. 2016 May;113(6):672-7. doi: 10.1002/jso.24215. Epub 2016 Mar 14.
• Background Zhong BY, Ni CF, Chen L, Zhu HD, Teng GJ. Early Sorafenib-related Biomarkers for Combination Treatment with Transarterial Chemoembolization and Sorafenib in Patients with Hepatocellular Carcinoma. Radiology. 2017 Aug;284(2):583-592. doi: 10.1148/radiol.2017161975. Epub 2017 Mar 6.
• Background Yao Q, Zhang H, Xiong B, Zheng C. Combination of sorafenib and TACE inhibits portal vein invasion for intermediate stage HCC: a single center retrospective controlled study. Oncotarget. 2017 Sep 8;8(45):79012-79022. doi: 10.18632/oncotarget.20745. eCollection 2017 Oct 3.
• Background Zhu K, Huang J, Lai L, Huang W, Cai M, Zhou J, Guo Y, Chen J. Medium or Large Hepatocellular Carcinoma: Sorafenib Combined with Transarterial Chemoembolization and Radiofrequency Ablation. Radiology. 2018 Jul;288(1):300-307. doi: 10.1148/radiol.2018172028. Epub 2018 Apr 24.
• Background Lei XF, Ke Y, Bao TH, Tang HR, Wu XS, Shi ZT, Lin J, Zhang ZX, Gu H, Wang L. Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study. World J Clin Cases. 2018 May 16;6(5):74-83. doi: 10.12998/wjcc.v6.i5.74.
• Background Ren B, Wang W, Shen J, Li W, Ni C, Zhu X. Transarterial Chemoembolization (TACE) Combined with Sorafenib versus TACE Alone for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Study. J Cancer. 2019 Jan 29;10(5):1189-1196. doi: 10.7150/jca.28994. eCollection 2019.
• Background Qin S, Bi F, Gu S, Bai Y, Chen Z, Wang Z, Ying J, Lu Y, Meng Z, Pan H, Yang P, Zhang H, Chen X, Xu A, Cui C, Zhu B, Wu J, Xin X, Wang J, Shan J, Chen J, Zheng Z, Xu L, Wen X, You Z, Ren Z, Liu X, Qiu M, Wu L, Chen F. Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial. J Clin Oncol. 2021 Sep 20;39(27):3002-3011. doi: 10.1200/JCO.21.00163. Epub 2021 Jun 29.

Drugs

Indications