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

NCT05161143 | Unknown Phase 2 DMC

• 1 other identifier: SH3137
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; Adjuvant therapy; Donafenib

Outcome Measures

Primary Outcomes (1)

• 1 year RFS rate

  1 year relapse-free survival rate

  1 year

Secondary Outcomes (6)

• RFS

  3 years

• OS

  3 years

• TTR

  3 years

• 2/3 year RFS rate

  2/3 years

• AE

  3 years

Study Arms (1)

Experimental: Donafenib plus TACE

EXPERIMENTAL

Donafenib: 4-8 weeks after radical surgery,patients will take donafenib, 200mg Bid,at least 6 months. TACE:4-8 weeks after radical surgery,Patients will receive TACE once.

Drug: Donafenib

Interventions

Donafenib DRUG

Donafenib: 4-8 weeks after radical surgery,patients will take donafenib, 200mg Bid,at least 6 months. TACE:4-8 weeks after radical surgery,patients will receive TACE once.

Also known as: TACE

Experimental: Donafenib plus TACE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 \~ 75 years old (including boundary value), male and female;
• Radical resection of liver cancer and intraoperative ablation of tumors ≤ 2cm were performed 4 \~ 8 weeks before enrollment;
• Hepatocellular carcinoma diagnosed by pathology and meeting at least one of the following conditions:
• Single tumor with tumor size ≥ 5cm;
• Pathology showed microvascular invasion (MVI);
• Satellite foci were found in the specimens;
• Multiple lesions (≥ 3);
• AFP ≥ 400 ng / ml one week before operation
• Preoperative imaging and / or intraoperative or postoperative pathological reports found PVTT type I: tumor thrombus invaded the secondary and above branches of portal vein;
• No anti-tumor treatment was received before operation;
• Liver function grade child Pugh a;
• Physical condition (PS) score of Eastern cancer cooperation group (ECoG) was 0-1;
• Imaging examination ≥ 4 weeks after operation confirmed that there was no recurrence and metastasis;
• The estimated survival time shall not be less than 3 months;
• With sufficient organ function reserve, the laboratory test values within 14 days before treatment must meet the following standards:

You may not qualify if:

• The pathological diagnosis was fiberboard HCC, sarcomatoid HCC, hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC);
• Positive margin or tumor rupture;
• Reoperation of recurrent liver cancer;
• Previous liver transplantation;
• AFP did not return to normal at 4 weeks and did not return to normal at 6 weeks after operation;
• Previously received systemic therapy for HCC, including targeted drug therapy such as Sorafenib, Lenvatinib and Regorafenib, or immunotherapy such as anti-PD-1, anti-PD-L1 and anti-CTLA-4, except antiviral therapy; If the patient has previously used traditional Chinese medicine with anti-tumor indications, it must be more than 4 weeks after the completion of treatment and before the medication in this study, and the adverse events caused by treatment have not recovered to ≤ CTCAE level 1;
• Received other adjuvant therapy (except antiviral therapy), including adjuvant local therapy;
• There were tumor thrombi in the main portal vein and primary branches, inferior vena cava, hepatic vein or bile duct, lymph node invasion or extrahepatic metastasis before operation;
• years of suffering from other malignancies, unless the patient has received the possibility of curative treatment and there is no evidence of the disease within 5 years, the time requirement (i.e. 5 years) does not apply to successful basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other orthotopic cancer.
• Previous history of severe mental illness;
• Suffering from diseases affecting the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc.);
• Taking drugs that may prolong QTc and / or induce tip twist transition ventricular tachycardia (TDP) or drugs that affect drug metabolism at the same time;
• The patient has known or suspected allergy to tyrosine kinase inhibitor (TKI) drugs, or is allergic to the excipients of the study drugs;
• There are uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion;
• Have active bleeding or abnormal coagulation function, have bleeding tendency or are receiving thrombolytic, anticoagulant or antiplatelet therapy;

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: collaborator

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

Beijing, China

Location

Related Publications (23)

• 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.

  PMID: 15761078 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.

  PMID: 26808342 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.

  PMID: 31648568 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.

  PMID: 31391767 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.

  PMID: 19034578 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.

  PMID: 22424438 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.

  PMID: 31303533 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.

  PMID: 29151695 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.

  PMID: 21488914 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.

  PMID: 29995763 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.

  PMID: 29420221 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.

  PMID: 29728879 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.

  PMID: 11413528 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.

  PMID: 31256949 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.

  PMID: 31081401 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.

  PMID: 28276833 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.

  PMID: 30305149 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.

  PMID: 33162826 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.

  PMID: 31897617 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.

  PMID: 17330237 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.

  PMID: 33425729 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.

  PMID: 26361969 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

donafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Yilei Mao, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haifeng XU, doctor

CONTACT

186 1043 1165; xuhf781120@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: December 17, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: December 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)