Adjuvant Therapy With Anlotinib for HCC

Study Overview
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Brief Summary
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Patients with high risk of disease recurrence after curative resection for hepatocellular carcinoma (HCC) deserve active intervention. However, there's limited treatment choice for these patients. Anlotinib hydrochloride, a multitarget tyrosine kinase inhibitor for both tumor angiogenesis and proliferative signaling in cancer cells, is approved in China for the 3rd line treatment of advanced non-small cell lung cancer. In the current study, we are to evaluate the safety and effects of adjuvant anlotinib therapy for the patients who underwent curative resection for HCC with high risk of tumor recurrence, which is defined by Shanghai Score (Sun, et al. Chin Med J (Engl) 2017).

Detailed Description
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Patients with high risk of disease recurrence after curative resection for hepatocellular carcinoma (HCC) deserve active intervention. However, there's limited treatment choice for these patients. Anlotinib hydrochloride, a multitarget tyrosine kinase inhibitor for both tumor angiogenesis and proliferative signaling in cancer cells, is approved in China for the 3rd line treatment of advanced non-small cell lung cancer. In the current study, we are to evaluate the safety and effects of adjuvant anlotinib therapy for the patients who underwent curative resection for HCC with high risk of tumor recurrence, which is defined by Shanghai Score (Sun, et al. Chin Med J (Engl) 2017). The primary outcome of this study is treatment safety, and the secondary outcome is recurrence-free survival and overall survival.

Official Title
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Adjuvant Therapy With Anlotinib Hydrochloride for Patients With Hepatocellular Carcinoma Who Underwent Curative Resection: a Single Arm Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Anlotinib Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged from 18-75 years. HCC diagnosis was confirmed by pathological examination and those who did not receive anti-tumor treatment (anti-tumor treatment including but not limited to: local ablation therapy, TACE, radiation therapy, chemotherapy, targeted drug therapy, immunotherapy, and etc.) Underwent curative resection for HCC with high risk of tumor recurrence, which was defined by Shanghai Score ≥ 4.922 (Sun, et al. Chin Med J (Engl) 2017) Child-Pugh class: A or B7 The ECOG Performance Status: 0-1 points The expected survival time ≥ 6 months No disease recurrence 4-6 weeks after surgery as evaluated by abdominal contrast-enhanced CT/MRI and chest CT. Adequate organs function Complete blood counting HB ≥ 90 g/L ANC ≥ 1.5×10^9 /L PLT ≥ 75×10^9/L Blood biochemistry ALB ≥ 28 g/L ALT and AST< 5×ULN TBIL ≤ 2×ULN Serum creatinine ≤ 1×ULN Women of childbearing age must have pregnancy tests within 7 days prior to admission, and the results are negative and are willing to use appropriate methods of contraception at 8 weeks after the trial and at the end of the trial. For men, surgical sterilization should be applied, or consent to use appropriate methods of contraception 8 weeks after the trial and at the end of the trial. Subjects voluntarily participated in the study, signed informed consent, good compliance in drug therapy and followed up. Exclusion Criteria: Cholangiocarcinoma, the combination of cholangiocarcinoma of HCC, or fibrolamellar HCC diagnosed by pathology examination. Past or current diagnosed with other malignancy, except skin basal cell carcinoma and cervical carcinoma in situ. Those treated with liver or other organ transplantation or willing to undergo liver transplantation. The conditions not suitable for oral medications, including difficulty swallowing, chronic diarrhoea, or bowel obstruction. Vascular events within 6 months, including stroke and transient ischemic attack , deep venous thrombosis or pulmonary artery embolism. Alimentary tract hemorrhage or high risk of alimentary tract hemorrhage due to esophageal varices, active ulcerative lesions or ulcerative colitis; or fecal occult blood test ≥ ++, or for those with fecal occult blood test (+), gastroscopy is required. Abnormal coagulation function (international normalized ratio > 2, prothrombin time > 16 s, thrombin time >21s, activated partial thromboplastin time > 21 s, or fibrinogen < 2 g/L); or other conditions with bleeding tendency or undergoing thrombolysis or anticoagulant therapy. Other severe or uncontrolled comorbidities: hypertension and the blood pressure was not well managed by medications (systolic pressure ≥ 150 mmHg or diastolic pressure ≥ 90 mmHg); level 2 or higher myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥ 480 ms); level 1 heart dysfunction; or LVEF < 50%. active or uncontrolled infection. uncontrolled diabetes (fasting blood glucose > 10 mmol/L). Urinary protein ≥ ++ or 24 hours urine protein > 1 g. Unhealed wounds, ulcer, or bone fracture. Those with mental illness or a history of psychotropic substance abuse; HIV infection. Other conditions that the investigators considered that not suitable for trial inclusion.

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: Anlotinib Hydrochloride<br>Oral anlotinib 12 mg/d | Drug: Anlotinib Hydrochloride<br>* Oral anlotinib hydrochloride 12 mg/d<br>* Other names: AL3818;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events rate | The rates of severity and seriousness of the adverse events. Adverse events are graded according to the NCI-CTCAE (Version 5.0) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival | From the date of liver surgery to the date of diagnosis of tumor recurrence or death from any cause | 24 months | 
| Overall survival | From the date of liver surgery to the date of death from any cause | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, anlotinib, adjuvant, surgery