Efficacy and Safety of Lenvatinib as an Adjuvant Therapy for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Lenvatinib is the standard of care for patients with advanced hepatocellular carcinoma (HCC). The aim of the single-arm, open-label, phase II clinical trial is to evaluate the efficacy and safety of lenvatinib as an adjuvant therapy for patients underwent radical resection of HCC with a high risk of tumor recurrence. Investigator hypothesize that lenvatinib may be an effective adjuvant treatment for HCC, and 12-month adjuvant treatment with lenvatinib can improve one-year recurrence-free survival rate (RFS) of HCC patients after surgical resection.

Detailed Description
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There's no widely accepted adjuvant therapy for patients with HCC. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, was approved for advanced or unresectable HCC. In this study, investigators aim to evaluate the effects and safety of adjuvant apatinib therapy for the patients who underwent curative resection for HCC with high risk of disease recurrence. Participants who underwent radical resection for HCC with high risk of tumor recurrence will be recruited in this study. During 4 to 6 weeks after surgery, each participant will receive a screening visit to exclude residual tumors. Each eligible participant will be treated with lenvatinib until tumor recurrence, intolerant adverse effect, participant' refusal, or completing 12-month treatment.

Official Title
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Safety and Efficacy of Lenvatinib as an Adjuvant Therapy in Patients With Hepatocellular Carcinoma Following Radical Resection: A Single-Arm and Open-Label Prospective Study

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Drug: Lenvima 4 mg Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 18-75; Histological diagnosis of HCC; Tumor stage before surgery: IIb/IIIa stage (>3 tumor nodules, or vascular invasion) HCC according to China Liver Cancer Staging System (or BCLC B/C/PVTT); Underwent R0 resection (microscopic or macroscopic tumor clearance) in four to six weeks before recruitment; no residual tumor before recruitment by imaging study (MRI/CT), nor metastases to other organs; Adequate liver, renal functions; Written informed consent; ECOG 0-1 and Child-Pugh A. Exclusion Criteria: WBC<4.0*10^9/L, HB<80 g/L, and PLT<75*10^9/L at blood screening; Coagulation function: (prothrombin time) international normalized ratio (INR) >2.3, or extension of prothrombin time>6 seconds; Liver function: serum albumin (ALB)<2.8 g/dl, total bilirubin (TBIL)>51.3μmol/L, alanine aminotransferase and aspartate aminotransferase (ALT and AST)>5 times the upper limit of normal range; Renal function: serum creatinine (Cr)>1.5 times the upper limit of normal range; lymph node metastases; The participant has uncontrolled ascites, hepatic encephalopathy, Gilbert's syndrome, and sclerosing cholangitis, etc.; The participant was included in other clinical trials 30 days before the selection; Other conditions that the investigators considered that not unsuitable for 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: Lenvatinib Arm<br>Experimental: Participants will be given lenvatinib (12 mg/d for body weight≥60kg, 8 mg/d for body weight < 60kg) for 12 months until disease recurrence or intolerance AEs or death. | Drug: Lenvima 4 mg Oral Capsule<br>* The participants will receive treatment with lenvatinib for 12 months after recruitment or until disease recurrence, intolerance AEs, or death. In case of treatment-related adverse effects, interruption or reduction is allowed.<br>* Other names: Lenvatinib 4 mg Oral Capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year RFS rate | 1-year RFS rate is defined as the percentage of patients who do not experience tumor recurrence or death from any cause after 1-year treatment. | 1 year after LPI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The duration from the date of first dosage to the date of death from any cause. | 3 years | 
| Adverse events | An adverse event (AE) refers to any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, but which does not necessarily have a causal relationship with this treatment. Number and classification of participants with treatment-related adverse events as assessed by CTCAE v4.0 were recorded. | 13 months | 
| Serious adverse events(SAE) | A serious adverse event (SAE) refers to an event in clinical trials that requires inpatient hospitalization or causes prolongation of existing hospitalization, permanent disability, incapacity, threats to life or death, and birth defect, etc. Number and classification of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 were recorded. | 13 months | 
| Health-related quality of life | Health-related quality of life questionnaire measured by EORTC QLQ-HCC18. | 13 months |