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

Sponsor

Jia Fan (Other)

Overall Status

Unknown status

CT.gov ID

NCT02281266

Collaborator

SciClone Pharmaceuticals (Industry)

360

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Curable Hepatitis B Virus-Related Hepatocellular Carcinoma	Procedure: curative resection Drug: thymalfasin Drug: nucleoside analog (suggest to use entecavir)	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Investigator Initiated Study of Thymosin in HBV-related HCC

Study Start Date :

Jan 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment (T) 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 Drug: thymalfasin 1.6mg twice a week, 12 months Other Names: ZADAXIN Drug: nucleoside analog (suggest to use entecavir)
Other: control (C) 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 Drug: nucleoside analog (suggest to use entecavir)

Arm

Intervention/Treatment

Experimental: treatment (T)

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

Drug: thymalfasin

1.6mg twice a week, 12 months

Other Names:

ZADAXIN

Drug: nucleoside analog (suggest to use entecavir)

Other: control (C)

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

Drug: nucleoside analog (suggest to use entecavir)

Outcome Measures

Primary Outcome Measures

Recurrence-free Survival [2-year]

Secondary Outcome Measures

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 [tumor sample will be collected at baseline and when relapse]
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)
incidence and types of Adverse Events (AE) and serious adverse event (SAE) [2-year]
AE and SAE will be reported. The number of patients with AE and the number of patients with SAE will be calculated.
number of patients with abnormal laboratory value, vital signs and ECG result [2-year]
The number of patients with abnormal laboratory value, vital signs and ECG result during the study will also be calculated.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.