Thymalfasin Adjuvant Therapy in Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma (HCC) After Curative Resection

Study Overview
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Brief Summary
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Efficacy and safety of Thymalfasin adjuvant therapy in HBV-related HCC after curative resection.

Detailed Description
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Multi-center, Randomized, Controlled Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Thymalfasin Therapy in Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma After Curative Resection.

Official Title
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Investigator Initiated Study of Thymosin in HBV-related HCC

Conditions
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Curable Hepatitis B Virus-Related Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: curative resection
* Drug: thymalfasin
* Drug: nucleoside analog (suggest to use entecavir)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria during perioperative period Male or female patients with age between 18-70 years. Life expectance ≥ 3 months. Diagnosis of Hepatocellular Carcinoma confirmed by Histological or Cytological examination. Hepatitis B history with current HBsAg positive and/or HBV DNA positive Will undergo hepatic curative resection. Tumor feature a. with cancer embolus b. a solitary nodule measuring between 3-8 cm or 2 nodule, a total combined measurement between 3-8 cm East Cooperative Oncology Group performance score of 0-2 Normal liver function or sufficient liver function, defined as Chlid's-Pugh A Inclusion criteria at baseline post-operation (4weeks ± 7days post-operation) No documented evidence of disease recurrence with computed tomography (CT) scan and CT angiography. Grade A of Chlid's-Pugh score hematological test white blood cell (WBC)>3.5X109/L, red blood cell (RBC)>30%, platelet count (PLT)>50,000/Ul, neutrophil (NEU)>1.0X109/L, Cr<1.5 mg/dl signed informed consent Exclusion Criteria: Any anti-cancer therapy, including liver transplant, transarterial Chemo-embolization (TACE), image-guided tumor ablation, radiotherapy, chemotherapy, molecular targeted therapy and immunotherapy, etc. prior to the liver surgery procedure. Taking the hepatotoxic drug or immunosuppressant drug. Invasion of portal vascular and its first branch, hepatic duct and its first branch, inferior vena cava and hepatic vein. Organ transplant recipient. Extra-hepatic organs and lymph node metastasis. Uncontrolled Hypertension, unstable angina within 3 months, congestive heart failure (New York Heart Association (NYHA) Class II or greater), history of myocardial infarction within 6 months prior to randomization and severe arrhythmia need to be treated. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix Known human immune deficiency virus (HIV) infection hepatitis C virus (HCV) infection History of stroke or transient ischemic attack within 6 months prior to randomization Active or untreated central nervous system (CNS) metastasis History of clinically significant drug or alcohol abuse Prior treatment with immunomodulator (e.g. interferon, Thymalfasin) or traditional Chinese medicine within 30 days prior to randomization Know postoperative complications (e.g. infection, bleeding, bile leak) at baseline Known allergic reaction to the investigational product and its excipient. Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study. The investigator considers the subject, for any reason, to be unacceptable for study participation. Participating in other clinical trials of the drug or medical device within 30 days prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment (T)<br>The patients of treatment arm will be administered subcutaneously Thymalfasin at dose of 1.6mg twice a week for 12 months after curative resection, followed by 12 months observation. Nucleoside analog plan to give to HBV DNA positive patients. | Procedure: curative resection<br> <br> Drug: thymalfasin<br>* 1.6mg twice a week, 12 months<br>* Other names: ZADAXIN;Drug: nucleoside analog (suggest to use entecavir)<br> <br> |
| Other: control (C)<br>The patients of control arm will be followed up for 2 years periodically after curative resection, without the investigational product (Thymalfasin) therapy. Nucleoside analog plan to give to HBV DNA positive patients. | Procedure: curative resection<br> <br> Drug: nucleoside analog (suggest to use entecavir)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival |  | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival (RFS) |  | 1-year | 
| Overall survival (OS) |  | 1-year | 
| Overall survival (OS) |  | 2-year | 
| Mean recurrence time |  | up to 2 years | 
| Tumor sample immune cell counts | immune cell counts includes T cell counts(CD3, CD4, CD8), Treg count(FoxP3), Th17 cell count(IL-17), natural killer(NK) cell count(CD56), neutrophil count(CD66b), Mφ count(CD68), dendritic cell(DC) count (CD1a,CD83), MVD(CD31) | tumor sample will be collected at baseline and when relapse | 
| incidence and types of Adverse Events (AE) and serious adverse event (SAE) | AE and SAE will be reported. The number of patients with AE and the number of patients with SAE will be calculated. | 2-year | 
| number of patients with abnormal laboratory value, vital signs and ECG result | The number of patients with abnormal laboratory value, vital signs and ECG result during the study will also be calculated. | 2-year |