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

Hepatocellular Carcinoma Clinical Trial

Official title:

A Prospective Cohort Study of the Effect of Lenvatinib Combined With TACE in Preventing the Recurrence in High-risk Patients With Hepatocellular Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03838796
• Other study ID #: Huashan 004
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 3, 2019
• Est. completion date: June 2023

Study information

• Verified date: July 2022
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 297
• Est. completion date: June 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Recurrence

Intervention

Drug:
• lenvatinib
for patients <60kg, lenvatinib 8mg bid po for patients >60kg, lenvatinib 12mg bid po

Procedure:
• TACE
The patient underwent transfemoral hepatic artery angiography one month after surgery to observe whether there was tumor staining in the liver. If there was suspicious tumor staining, micro-catheter was superselected to the tumor blood vessel, the embolization agents and chemotherapy drugs were injected. If there was no tumor staining, a small amount of embolization agents were slowly injected into the artery.

Locations

Country	Name	City	State
China	Huashan hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (4)

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 o — View Citation

Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003 Dec 6;362(9399):1907-17. Review. — View Citation

Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-relat — View Citation

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 C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival	the survival time after liver resection without tumor recurrence or metastasis	2 years
Secondary	Overall survival	the survival time after liver resection	5 years