Donafenib Combined With TACE as Adjuvant Therapy of Patients With Hepatocellular Carcinoma

Summary

The investigators design a phase IIB clinical study to explore the efficacy and safety of Donafenib combined with TACE as adjuvant therapy of patients with hepatocellular carcinoma at a high risk of recurrence after radical resection.

Timeline

Start

2021-12

Primary completion

2023-12

Completion

2024-12

Publications

• Background Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108. doi: 10.3322/canjclin.55.2.74.
• Background Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
• Background Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol. 2019 Nov;13(11):1077-1088. doi: 10.1080/17474124.2019.1684898. Epub 2019 Oct 30.
• Background Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol. 2019 Jul 28;25(28):3704-3721. doi: 10.3748/wjg.v25.i28.3704.
• Background Cucchetti A, Piscaglia F, Caturelli E, Benvegnu L, Vivarelli M, Ercolani G, Cescon M, Ravaioli M, Grazi GL, Bolondi L, Pinna AD. Comparison of recurrence of hepatocellular carcinoma after resection in patients with cirrhosis to its occurrence in a surveilled cirrhotic population. Ann Surg Oncol. 2009 Feb;16(2):413-22. doi: 10.1245/s10434-008-0232-4. Epub 2008 Nov 26.
• Background European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.
• Background Shen A, Liu M, Zheng D, Chen Q, Wu Z. Adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2020 Apr;44(2):142-154. doi: 10.1016/j.clinre.2019.06.012. Epub 2019 Jul 11.
• Background Ye JZ, Chen JZ, Li ZH, Bai T, Chen J, Zhu SL, Li LQ, Wu FX. Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion. World J Gastroenterol. 2017 Nov 7;23(41):7415-7424. doi: 10.3748/wjg.v23.i41.7415.
• Background Wong JS, Wong GL, Tsoi KK, Wong VW, Cheung SY, Chong CN, Wong J, Lee KF, Lai PB, Chan HL. Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma. Aliment Pharmacol Ther. 2011 May;33(10):1104-12. doi: 10.1111/j.1365-2036.2011.04634.x. Epub 2011 Mar 24.
• Background Wu J, Yin Z, Cao L, Xu X, Yan T, Liu C, Li D. Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment: A meta-analysis. Medicine (Baltimore). 2018 Jul;97(28):e11295. doi: 10.1097/MD.0000000000011295.
• Background Wang Z, Ren Z, Chen Y, Hu J, Yang G, Yu L, Yang X, Huang A, Zhang X, Zhou S, Sun H, Wang Y, Ge N, Xu X, Tang Z, Lau W, Fan J, Wang J, Zhou J. Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin Cancer Res. 2018 May 1;24(9):2074-2081. doi: 10.1158/1078-0432.CCR-17-2899. Epub 2018 Feb 2.
• Background Liu S, Guo L, Li H, Zhang B, Sun J, Zhou C, Zhou J, Fan J, Ye Q. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol. 2018 Jul;25(7):2098-2104. doi: 10.1245/s10434-018-6438-1. Epub 2018 May 4.
• Background Ono T, Yamanoi A, Nazmy El Assal O, Kohno H, Nagasue N. Adjuvant chemotherapy after resection of hepatocellular carcinoma causes deterioration of long-term prognosis in cirrhotic patients: metaanalysis of three randomized controlled trials. Cancer. 2001 Jun 15;91(12):2378-85.
• Background Chen ZH, Zhang XP, Zhou TF, Wang K, Wang H, Chai ZT, Shi J, Guo WX, Cheng SQ. Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Eur J Surg Oncol. 2019 Nov;45(11):2188-2196. doi: 10.1016/j.ejso.2019.06.031. Epub 2019 Jun 25.
• Background Wang L, Ke Q, Lin N, Zeng Y, Liu J. Does postoperative adjuvant transarterial chemoembolization benefit for all patients with hepatocellular carcinoma combined with microvascular invasion: a meta-analysis. Scand J Gastroenterol. 2019 May;54(5):528-537. doi: 10.1080/00365521.2019.1610794. Epub 2019 May 12.
• Background Liao M, Zhu Z, Wang H, Huang J. Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis. Scand J Gastroenterol. 2017 Jun-Jul;52(6-7):624-634. doi: 10.1080/00365521.2017.1292365. Epub 2017 Feb 22.
• Background Wei W, Jian PE, Li SH, Guo ZX, Zhang YF, Ling YH, Lin XJ, Xu L, Shi M, Zheng L, Chen MS, Guo RP. Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond). 2018 Oct 10;38(1):61. doi: 10.1186/s40880-018-0331-y.
• Background Liu F, Guo X, Dong W, Zhang W, Wei S, Zhang S, Zhu X, Zhou W, Zhang J, Liu H. Postoperative adjuvant TACE-associated nomogram for predicting the prognosis of resectable Hepatocellular Carcinoma with portal vein Tumor Thrombus after Liver Resection. Int J Biol Sci. 2020 Oct 23;16(16):3210-3220. doi: 10.7150/ijbs.46896. eCollection 2020.
• Background Huo YR, Chan MV, Chan C. Resection Plus Post-operative Adjuvant Transcatheter Arterial Chemoembolization (TACE) Compared with Resection Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Cardiovasc Intervent Radiol. 2020 Apr;43(4):572-586. doi: 10.1007/s00270-019-02392-6. Epub 2020 Jan 2.
• Background Jiang H, Meng Q, Tan H, Pan S, Sun B, Xu R, Sun X. Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas. Int J Cancer. 2007 Jul 15;121(2):416-24. doi: 10.1002/ijc.22655.
• Background Yao W, Xue M, Lu M, Wang Y, Zhao Y, Wu Y, Fan W, Li J. Diffuse Recurrence of Hepatocellular Carcinoma After Liver Resection: Transarterial Chemoembolization (TACE) Combined With Sorafenib Versus TACE Monotherapy. Front Oncol. 2020 Dec 17;10:574668. doi: 10.3389/fonc.2020.574668. eCollection 2020.
• Background Chen JH, et al. 2020 ASCO. Poster 4580.
• Background Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.

Drugs

Indications