Clinical trial NCT04229355: DEB-TACE Plus Lenvatinib or Sorafenib or PD-1 Inhibitor for Unresectable Hepatocellular Carcinoma
Official title: Drug-eluting Bead Transarterial Chemoembolization Plus Lenvatinib or Sorafenib or PD-1 Inhibitor for Unresectable Hepatocellular Carcinoma: a Multicentric Prospective Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Lead sponsor: Guangxi Medical University
Sponsor class: OTHER
First posted: 2020-01-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Transarterial chemoembolization (TACE) based on drug-eluting beads (DEB-TACE) is widely used for unresectable hepatocellular carcinoma (HCC). However, the long-term survival is still low after DEB-TACE treatment. In recent years, lenvatinib and anti-PD-1 have exhibited potential therapeutic effects for advanced HCC. And sorafenib is the standard drug for advanced HCC. Combining targeted drugs or immunotherapies with DEB-TACE may provide synergistic effects and facilitate the development of personalized medicine. Therefore, this prospective study aims to investigate the safety and efficacy of DEB-TACE plus sorafenib or lenvatinib or PD-1 Inhibitor for unresectable HCC.

Detailed description: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Most patients with HCC are diagnosed as advanced stage or unresectable disease because of the lack of signs and symptoms. Despite significant research efforts, only a few effective treatment approaches have been developed for HCC. Conventional transarterial chemoembolization (cTACE) is widely used as a palliative treatment for inoperable HCC. TACE based on drug-eluting beads (DEB-TACE) has recently been introduced into the clinic. This technique relies on drug-loaded microspheres to embolize and release antitumor medication gradually and locally in order to maximize local ischemia and tumor necrosis. Nowadays, many RCTs and meta-analyses found DEB-TACE is associated with higher overall survival than cTACE for unresectable HCC. However, the long-term survival is still low after DEB-TACE treatment. In recent years, targeted drugs (such as sorafenib, lenvatinib) and immune checkpoint inhibitor (anti-PD-1) have exhibited potential therapeutic effects for advanced HCC. Lenvatinib is non-inferior to sorafenib in overall survival in untreated advanced HCC. Combining targeted drugs or immunotherapies with conventional therapeutic approaches may provide synergistic effects and facilitate the development of personalized medicine. However, it is still unknown which is the best combining treatment. Therefore, this prospective study aims to investigate the safety and efficacy of DEB-TACE plus sorafenib or lenvatinib or PD-1 Inhibitor for unresectable HCC.

Eligibility criteria: Inclusion Criteria:

* Age 18 - 75 years
* Patients with unresectable primary hepatocellular carcinoma.
* With Child-Pugh A liver function.

Exclusion Criteria:

* Patients received targeted drugs, anti-PD1, or anti-PD-L1 treatment.
* Patients with recurrent hepatocellular carcinoma.
* Patient compliance is poor.
* The blood supply of tumor lesions is absolutely poor or arterial-venous shunt that TACE can not be performed.
* Known history of human immunodeficiency virus (HIV) infection.
* Known Central Nervous System tumors including metastatic brain disease.
* Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
* History of organ allograft.
* Known or suspected allergy to the investigational agent or any agent given in association with this trial.
* Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
* Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.

Primary outcomes:
measure: Progression-free survival
timeFrame: one month
Secondary outcomes:
measure: Overall survival
timeFrame: one month
Other outcomes:
Locations:
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
Study officials:
affiliation: Guangxi Medical University Cancer Hospital
name: Le-Qun Li, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: Hatanaka T, Kakizaki S, Nagashima T, Namikawa M, Tojima H, Shimada Y, Takizawa D, Naganuma A, Arai H, Sato K, Harimoto N, Shirabe K, Uraoka T. Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study. Hepatol Res. 2020 Mar;50(3):382-395. doi: 10.1111/hepr.13460. Epub 2019 Dec 10.
citation: Kim JJ, McFarlane T, Tully S, Wong WWL. Lenvatinib Versus Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma: A Cost-Utility Analysis. Oncologist. 2019 Nov 20:theoncologist.2019-0501. doi: 10.1634/theoncologist.2019-0501. Online ahead of print.
citation: Feng Z, Rong P, Wang W. Meta-analysis of the efficacy and safety of PD-1/PD-L1 inhibitors administered alone or in combination with anti-VEGF agents in advanced hepatocellular carcinoma. Gut. 2020 Oct;69(10):1904-1906. doi: 10.1136/gutjnl-2019-320116. Epub 2019 Dec 18. No abstract available.
citation: Xie ZB, Wang XB, Peng YC, Zhu SL, Ma L, Xiang BD, Gong WF, Chen J, You XM, Jiang JH, Li LQ, Zhong JH. Systematic review comparing the safety and efficacy of conventional and drug-eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma. Hepatol Res. 2015 Jan;45(2):190-200. doi: 10.1111/hepr.12450. Epub 2014 Dec 24.