Lenvatinib Combined With TACE to Prevent the Recurrence in High-risk Patients With Hepatocellular Carcinoma

Not Applicable

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: lenvatinib; Procedure: TACE

• Registration Number: NCT03838796
• Lead Sponsor: Fudan University

Brief Summary

The purpose of the study is to observe the effect of Lenvatinib Combined With TACE in preventing the recurrence in high-risk patients with hepatocellular carcinoma.

Detailed Description

Postoperative recurrence and metastasis of hepatocellular carcinoma(HCC）is the main problem during the treatment. Although with the development of medical science, some drugs have been found for the prevention and treatment of postoperative recurrence of HCC (such as postoperative application of interferon to prevent early tumor recurrence), but there is still no drug widely recognized.

Transcatheter arterial chemoembolization (TACE) is a palliative treatment for hepatocellular carcinoma. TACE can detect the early recurrence of tumor after liver resection, and has a complementary treatment effect on hidden residual lesions. For patients with high-risk, the tumor recurrence rate can be significantly reduced, and the tumor-free survival can be prolonged by TACE. Therefore, patients with high-risk of recurrence after resection were routinely arranged TACE treatment as an adjuvant treatment after surgery.

Lenvatinib is a multi-target receptor tyrosine kinase inhibitor (TKI), which mainly inhibits vascular endothelial growth factor(VEGF) receptor-1, 2, 3; fibroblast growth factors(FGF) receptor-1, 2, 3, 4; platelet derived growth factor receptor(PDGFR)α; RET and KIT, thereby inhibiting tumor cell proliferation, inducing apoptosis, and acting as an anti-angiogenesis. The REFLECT study showed that the median overall survival(OS) of the patients in the lenvatinib group was 13.6 months (95% CI, 12.1-14.9) and that in the sorafenib group was 12.3 months (95% CI, 10.4-13.9) , which reached a non-inferiority end point (HR = 0.92; 95% CI, 0.79-1.06). In addition, all secondary endpoints in the lenvatinib group were significantly better than the sorafenib group. A subgroup analysis based on Chinese patients showed that the OS of Lenvatinib was significantly 4.8 months longer than sorafenib group (15.0 months vs 10.2 months). Other three secondary endpoints, progression-free survival(PFS) (9.2 months vs 3.6) and time to progression(TTP)(11.0 months vs 3.7 months) and objective response rate(ORR) (21.5% vs 8.3%), were also significantly better in Lenvatinib group. Based on the above datas, lenvatinib will become a new choice for Chinese patients with HCC. It has also been approved by the FDA and CFDA as the first-line treatment for patients with advanced HCC.

So, this study is to observe the effect of lenvatinib combined with TACE in preventing the recurrence in high-risk patients with HCC.

Study Timeline

• Study Start: 2019-01-03
• Study First Submitted: 2019-02-11
• Study First Submitted QC: 2019-02-11
• Study First Posted: 2019-02-12
• Primary Completion: 2022-06-30
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-29
• Last Update Posted: 2022-08-02
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 297

Inclusion Criteria

• The characteristics of the treatment history:

No lenvatinib treatment history, no sorafenib allergies.

• The characteristics of the tumor:

The pathological results is hepatocellular carcinoma.

Meet any of the following articles:

Pathological prompt microvascular invasion(MVI) class II, and incorporate any of the following:Tumor number≥3,Tumor size≥8cm,Tumor margin is not clear and no complete capsule.

With the embolus in Portal vein, hepatic vein or bile duct. Preoperative rupture or invasion the adjacent organs.

• The characteristics of the patients:

The patient age was between 18-75. The American Society of Anesthesiologists(ASA）score was I-III. The Child-pugh score was A. Total bilirubin≤3.0 mg/dL, albumin≥28 g/L, AST, ALT, ALP≤5 times the upper limit of normal value.

Routine blood test: the neutrophil≥1.5×10^9/L, Hb≥8.5g/L，PLT≥75×10^9/L. The INR≤2.3. The Eastern Cooperative Oncology Group(ECOG) score was less than 2 points

Exclusion Criteria

• R1/2 or palliative rescted tumor
• Pregnant or lactating women.
• Patients with other malignant tumor.
• Patients with mental illness.
• Patients participated in other clinical trials in last three months.
• Residual lesions showed by Postoperative digital subtraction angiography(DSA).
• Postoperative patients treated with other targeted drugs, PD1 antibody and other immunotherapies, FOLFOX systemic chemotherapy, and HuaiErKeLi drug treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lenvatinib and TACE	TACE	use lenvatinib and TACE after liver resection in HCC patients
lenvatinib	lenvatinib	use lenvatinib after liver resection in HCC patients
lenvatinib and TACE	lenvatinib	use lenvatinib and TACE after liver resection in HCC patients

Primary Outcome Measures

Name	Time	Method
Disease free survival	2 years	the survival time after liver resection without tumor recurrence or metastasis

Secondary Outcome Measures

Name	Time	Method
Overall survival	5 years	the survival time after liver resection

Trial Locations

Locations (1)

Huashan hospital; 🇨🇳 Shanghai, China