HAIC Sequential TAE Combined With Lenvatinib and Tislelizumab in Unresectable HCC

NCT05532319 | Completed Phase 2 DMC

• 1 other identifier: FRONT-1
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with unresectable hepatocellular carcinoma will receive hepatic arterial infusion chemotherapy (HAIC) sequential transarterial embolization combined with lenvatinib and tislelizumab.

Conditions

Liver Cancer

Keywords

hepatocellular carcinoma; hepatic arterial infusion chemotherapy; lenvatinib; tislelizumab

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The primary end-point is the progression-free survival rate per RECIST at six months

  6 months

Secondary Outcomes (2)

• Overall survival

  2 years

• objective response rate

  6 months

Study Arms (1)

HAIC sequential TAE combined with lenvatinib and tislelizumab

EXPERIMENTAL

The aim of this phase II trial is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) sequential transarterial embolization combined with lenvatinib and tislelizumab in patients with unresectable hepatocellular carcinoma (HCC), and to explore the optimal benefit population.

Combination Product: HAIC sequential TAE combined with lenvatinib and tislelizumab

Interventions

HAIC sequential TAE combined with lenvatinib and tislelizumab COMBINATION_PRODUCT

Patients with unresectable hepatocellular carcinoma will receive hepatic arterial infusion chemotherapy (HAIC) sequential transarterial embolization combined with lenvatinib and tislelizumab.

HAIC sequential TAE combined with lenvatinib and tislelizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCC is diagnosed in accordance with the clinical diagnostic criteria of the Guidelines for the Diagnosis and Treatment of primary liver Cancer (2019 edition) issued by the Health Commission of the People's Republic of China or by histopathology;
• ECOG PS 0 or 1;
• Child-Pugh A liver function;
• Chinese Liver Cancer (CNLC) stage IIb, IIIa and IIIb patients, or CNLC stage Ib and IIA patients who cannot undergo hepatectomy for various reasons;
• Expected survival time ≥6 months;
• HCC patients with incomplete portal vein obstruction or complete portal vein obstruction with abundant compensatory collateral vessels;
• Hematological indicators should meet the following conditions: hemoglobin ≥90 g/L; absolute neutrophil count ≥1.5×10\^9/L; platelets ≥80×10\^9/L; total bilirubin ≤1.5×ULN; ALT 3 x ULN or less; AST 3 x ULN or less; alkaline phosphatase ≤2.5×ULN; serum albumin ≥28 g/L; serum creatinine ≤1.5×ULN;
• Urinary protein \<2+ or 24 h urinary protein \< 1.0 g;
• For women of reproductive age, use of contraception (e.g. intrauterine devices, tablets or condoms) is required during the course of 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 before enrollment in the study; male patients with potential reproductive partners should use effective contraception during the study period and for 120 days after the study.

You may not qualify if:

• Previous or co-existing other malignancies except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
• Previously received HAIC, TACE, TAE, radiofrequency ablation and other local treatments for HCC;
• Patients who have received or are using one of the following three drugs in the previous 6 months: ① immune checkpoint inhibitors, including but not limited to artemizumab, nivolumab, pembrolizumab, camrelizumab, sintilimab, toripalimab, and tislelizumab; ② molecular targeted therapy, including but not limited to sorafenib, lenvatinib, apatinib, regorafenib, anlotinib, bevacizumab, etc. ③ systemic chemotherapy drugs (such as doxorubicin, oxaliplatin, 5-FU, S-1, etc.);
• Having a congenital or acquired immunodeficiency disease (e.g. being HIV positive);
• Active infection, or body temperature ≥ 38.5℃ or white blood cell count \> 15 x 10\^9/L 7 days before enrollment;
• Within 3 months of enrollment, patients with hemorrhagic diseases (including but not limited to moderate/severe esophageal and gastric variceal bleeding, gastrointestinal bleeding, hemorrhagic gastric ulcer, hemoptysis \> 2.5 mL per day; For positive cases of fecal occult blood, occult blood should be reexamined, and gastroenteroscopy should be performed if necessary);
• Arterial or venous thrombosis within 6 months, such as cerebrovascular accident (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, pulmonary infarction, etc.;
• Those who have a history of alcohol or psychotropic drug abuse and are unable to abstain or have mental disorders;
• Pregnant or lactating women;
• Active autoimmune diseases or previous autoimmune diseases (such as autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, etc.);
• Being treated with immunosuppressive agents or glucocorticoids (\>10mg prednisone/day) within 2 weeks;
• Complicated with hepatic encephalopathy or brain metastasis;
• Medically uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) (based on the average of BP readings obtained from ≥2 measurements);
• Uncontrolled heart disease or symptoms (including but not limited to cardiac function grade II or above, unstable angina pectoris, myocardial infarction in the previous 1 year, supraventricular or ventricular arrhythmias requiring treatment or intervention);
• Abnormal coagulation (INR \> 2.0, PT \> 16 s), bleeding tendency or need for thrombolytic therapy or anticoagulant therapy (although prophylactic use of low-dose aspirin or low molecular weight heparin is permitted);

Sponsors & Collaborators

• Guangxi Medical University: lead

Study Sites (1)

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530021, China

Location

Related Publications (4)

• Lai Z, He M, Bu X, Xu Y, Huang Y, Wen D, Li Q, Xu L, Zhang Y, Wei W, Chen M, Kan A, Shi M. Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: A biomolecular exploratory, phase II trial. Eur J Cancer. 2022 Oct;174:68-77. doi: 10.1016/j.ejca.2022.07.005. Epub 2022 Aug 15.

  PMID: 35981413 BACKGROUND

• Li QJ, He MK, Chen HW, Fang WQ, Zhou YM, Xu L, Wei W, Zhang YJ, Guo Y, Guo RP, Chen MS, Shi M. Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial. J Clin Oncol. 2022 Jan 10;40(2):150-160. doi: 10.1200/JCO.21.00608. Epub 2021 Oct 14.

  PMID: 34648352 BACKGROUND

• He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. doi: 10.1001/jamaoncol.2019.0250.

  PMID: 31070690 BACKGROUND

• Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). J Clin Oncol. 2022 Feb 10;40(5):468-480. doi: 10.1200/JCO.21.01963. Epub 2021 Dec 14.

  PMID: 34905388 BACKGROUND

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

lenvatinib; tislelizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Le-Qun Li, PhD

  Guangxi Medical University Cancer Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The aim of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) sequential transarterial embolization combined with lenvatinib and tislelizumab in patients with unresectable hepatocellular carcinoma (HCC), and to explore the optimal benefit population.

Study Record Dates

• First Submitted: September 4, 2022
• First Posted: September 8, 2022
• Study Start: November 10, 2022
• Primary Completion: December 23, 2025
• Study Completion: December 23, 2025
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)