TACE Combined With Tyrosine Kinase Inhibitors and Tislelizumab in Unresectable Hepatocellular Carcinoma

Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors and Tislelizumab in Unresectable Hepatocellular Carcinoma

Most hepatocellular carcinoma (HCC) are found in the intermediate or advanced stage. The patients lose the opportunity of curative surgical resection. In clinical practice, unresectable HCC is often encountered with large tumor lesions and insufficient remaining liver volume. It is expected that the benefit of direct surgical resection will not exceed that of non-surgical treatment if the tumor is limited in scope but with unclear boundaries, surrounding small foci, or adjacent to important vascular structures, or combined with secondary or higher portal vein tumor thrombus. These patients account for a significant proportion of unresectable HCC, but have the potential for surgical resection. If the investigators can make full use of the existing HCC treatment, the patients hope to obtain radical surgical resection opportunities and better long-term survival after tumor shrinkage and tumor necrosis boundary becomes clear.

Transcatheter arterial chemoembolization (TACE) has been the standard arterial treatment for advanced HCC. Tyrosine kinase Inhibitor is the first-line treatment for hepatocellular carcinoma. Tislelizumab is an immune checkpoint inhibitor and a first-line treatment for HCC. This study investigated the efficacy and safety of TACE combined with Tyrosine Kinase Inhibitors and tislelizumab in the treatment of unresectable HCC.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Transarterial chemoembolization combined with Tyrosine Kinase Inhibitors and Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Jian-Hong Zhong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Had Child-Pugh score 5-7 liver function, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function at the time of treatment initiation;
• With stage Ⅰb, Ⅱa, Ⅱb or Ⅲa hepatocellular carcinoma (HCC) based on the Chinese liver Cancer Staging System (CNLC);
• With unresectable HCC because of insufficient residual liver volume;
• Expected survival time ≥6 months;
• Hematology indexes should meet the following conditions: hemoglobin ≥90 g/L; platelet ≥80; total bilirubin ≤1.5×ULN; alanine transaminase ≤3×ULN; aspertate aminotransferase ≤ 3 x ULN; alkaline phosphatase ≤2.5×ULN; serum albumin ≥28 g/L; serum creatinine ≤1.5×ULN;
• Urinary protein <2+ or 24 h urinary protein quantity < 1.0g;
• For women of reproductive age, contraceptive measures (such as intrauterine devices, contraceptive tablets or condoms) are required during the clinical trial until 120 days after the end of the clinical trial; Women of childbearing age had negative serum or urine HCG test results within 7 days prior to inclusion in the study; For male patients whose partners have reproductive potential, effective contraception should be used during the study period and for 120 days after the end of the study.

Exclusion Criteria:

• Combined with other malignant tumors;
• Previously received local treatment of HCC such as Hepatic Artery Infusion Chemotherapy, transarterial (chemo)embolization, or local ablation;
• Those who have received or are using one of the following three types of drugs in the past 6 months: Immune checkpoint inhibitors, including but not limited to Atezolizumab, Nivolumab, pembrolizumab, Camrelizumab, Tislelizumab, triplizumab, sintilimab, etc.; Molecular targeted therapy, including but not limited to sorafenib, lenvatinib, donafenib, apatinib, regorafenib, anrotinib, bevacizumab, etc.; systemic chemotherapy drugs (such as doxorubicin, oxaliplatin, 5-FU, S-1, etc.);
• The presence of congenital or acquired immunodeficiency diseases (such as HIV positive);
• Active infection, or body temperature ≥ 38.5℃ 7 days before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transarterial chemoembolization combined with Tyrosine Kinase Inhibitors and Tislelizumab; Patients with unresectable hepatocellular carcinoma were received transarterial chemoembolization combined with Tyrosine Kinase Inhibitors and Tislelizumab	Drug: Transarterial chemoembolization combined with Tyrosine Kinase Inhibitors and Tislelizumab; Patients with unresectable hepatocellular carcinoma were received transarterial chemoembolization combined with Tyrosine Kinase Inhibitors and Tislelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The proportion of progression-free survival in one year	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The proportion of overall survival in one year	One year

Collaborators and Investigators

• Sponsor: Guangxi Medical University
• Investigators: Principal Investigator: Shao-Ping Liu, M.D, The Eighth Affiliated hospital of the Guangxi Medical University

Publications and helpful links

General Publications

• Chen K, Wei W, Liu L, Deng ZJ, Li L, Liang XM, Guo PP, Qi LN, Zhang ZM, Gong WF, Huang S, Yuan WP, Ma L, Xiang BD, Li LQ, Zhong JH. Lenvatinib with or without immune checkpoint inhibitors for patients with unresectable hepatocellular carcinoma in real-world clinical practice. Cancer Immunol Immunother. 2022 May;71(5):1063-1074. doi: 10.1007/s00262-021-03060-w. Epub 2021 Sep 24.
• 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.
• Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11.
• Qin S, Kudo M, Meyer T, Bai Y, Guo Y, Meng Z, Satoh T, Marino D, Assenat E, Li S, Chen Y, Boisserie F, Abdrashitov R, Finn RS, Vogel A, Zhu AX. Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Dec 1;9(12):1651-1659. doi: 10.1001/jamaoncol.2023.4003.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): January 20, 2024

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: January 22, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Tislelizumab; Tyrosine Kinase Inhibitors
• Other Study ID Numbers: FRONT-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Original data can be obtained from the corresponding authors in accordance with privacy/ethical restrictions.
• IPD Sharing Time Frame: After the full paper was published.
• IPD Sharing Access Criteria: use the data for further analysis, for example, meta-analysis.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No