Anlotinib Combined With TACE in Hepatocellular Carcinoma Patients at High Risk of Post Surgery Recurrence

Study Overview
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Brief Summary
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A single-arm, open-label clinical trial to assess the effects and safety of anlotinib hydrochloride combined with transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma(HCC) patients at high risk of post surgery recurrence.

Detailed Description
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Hepatocellular carcinoma is one of the most common malignant tumors in the world with high incidence and mortality. Recurrence of HCC is still a great challenge and threat to the patients after resection surgery. Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. HCC patients who meet the eligibility criteria of this clinical trial will adopt postoperative TACE combined with anlotinib hydrochloride. At Day4 of TACE,anlotinib 12mg QD PO d1-14, 21 days per cycle until disease progresses or intolerant. Primary Efficacy Endpoint: Disease free survival (DFS);Secondary Efficacy Endpoints: 1-year DFS Rate and Time to recurrence (TTR)(According to RECIST Version 1.1).Safety will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.

Official Title
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An Open, Single Arm,Multicenter Clinical Trial of Anlotinib Combined With Transcatheter Arterial Chemoembolization for Adjuvant Therapy in Patients With High Risk of Recurrence After Resection of Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma, TACE, Anlotinib

Intervention / Treatment
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* Drug: Anlotinib Hydrochloride
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients participate in the study voluntarily and sign informed consent with good compliance. After hepatectomy, satisfy any of the following recurrence factors was assessed:≥5 cm and < 10 cm of tumor diameter; tumor number≥3; tumor microvascular invasion grade M1; portal vein carcinoma thrombus resection(Ⅰ、Ⅱ). Histological or cytological confirmation of hepatocellular carcinoma, or at least two imaging tests with hepatocellular carcinoma characteristics, or one imaging test with hepatocellular carcinoma characteristics and AFP > 400μg/L. TACE treatment (cTACE only) was completed within 1-2 months after hepatectomy. ≥ 18 and ≤ 75 years of age. ECOG performance status of 0-1. liver function child-Pugh class A or B (≤7 points). Except for hepatectomy, no previous tumor-related treatment was received, and the remaining liver was assessed to have good liver function. Exclusion Criteria: Patients who have had or are currently complicated with other malignant tumors,or recurrent hepatocellular carcinoma (>10 mm)in baseline data or in TACE. Patients with absolute contraindications to TACE. Patients with HCV infection. Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0 g confirmed. Pregnant or lactating women. Patients with mental illness.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Administration anlotinib and it should be continued until relapse of HCC or intolerable toxicity or patients withdrawal of consent. | Drug: Anlotinib Hydrochloride<br>* Anlotinib 12mg QD PO d1-14, 21 days per cycle.<br>Procedure: TACE<br>* TACE first, followed by anlotinib within day4（+/-1days）<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | The period from resection surgery to recurrence of HCC | From randomization to recurrence of HCC or death (up to 1year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year DFS Rate | One year ratio of DFS | From randomization to recurrence of HCC or death (up to 1year) | 
| Time to recurrence | The period from resection surgery to recurrence of HCC | From randomization to recurrence of HCC(up to 1year) | 
| Incidence of Treatment-Emergent Adverse Events Safety and Tolerability | Any adverse effects occur during the use of anlotinib | Up to 30 day safety follow-up visit |