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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: lenvatinib
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: lenvatinib<br>use lenvatinib after liver resection in HCC patients | Drug: lenvatinib<br>* for patients <60kg, lenvatinib 8mg bid po for patients >60kg, lenvatinib 12mg bid po<br>* Other names: lenvatinib treatment;|
| Active Comparator: lenvatinib and TACE<br>use lenvatinib and TACE after liver resection in HCC patients | Drug: lenvatinib<br>* for patients <60kg, lenvatinib 8mg bid po for patients >60kg, lenvatinib 12mg bid po<br>* Other names: lenvatinib treatment;Procedure: TACE<br>* 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.<br>* Other names: transcatheter arterial chemoembolization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | the survival time after liver resection without tumor recurrence or metastasis | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | the survival time after liver resection | 5 years |