Expanding Phase III Study of Tyroserleutide for Injection

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blinded, placebo-controlled, multi-center Clinical Trial. Patients with no tumor lesions 21 days after resection of hepatocellular carcinoma will be randomized in a 1:1 ratio to 1 of the 2 treatment groups：6mg/d Tyroserleutide (injection), or placebo

Detailed Description
-----------------
The first stage includes evaluation of subjects, to assess the inclusion criteria and exclusion criteria, based on the patients' preoperative imaging results, including tumor size, tumor characteristics, etc. In the second stage, subjects will return to the hospital 21 days following the baseline examination.The investigator will determine whether the subject satisfies all inclusion/exclusion criteria. If all requirements are satisfied, then randomization will occur 21 days after surgery The day of randomization will be defined as Day 0. Randomized subjects will return to the hospital and begin cycle 1 on the day of randomization (Day 0). and the relevant laboratory tests will be performed within 3 days after the end the study drug infusion. Cycles will occur as follows: cycles 2, 3, 4, 5, and n will begin on days 42±3, 70±3, 98±3, 126±3, and 14+28（n-1)± 3, respectively. Based therapeutic drugs are Gan Fu Le the participant will receive medical inspection so as to observe and ensure drug safety.

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled, Multicenter Expanding Phase III Clinical Trial to Evaluate the Safety and Efficacy of Injectable Tyroserleutide to Treat Hepatocellular Carcinoma (HCC) (After HCC Resection)

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: Gan Fu Le Tablets
* Drug: Tyroserleutide for injection
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Aged ≥ 18 years and ≤ 75 years old, male or female Subject underwent resection of hepatocellular carcinoma (confirmed by pathology) The tumor characteristics must meet the following:A single tumor with a maximum diameter >5cm ,Preoperative imaging, or Intraoperative visual observation.; Exclusion Criteria: Concomitant malignant tumor(s) in other systems is/are present Tumor thrombosis in the branch of portal vein or in hepatic vein is detected by preoperative imaging or observed during the surgery The subject received any previous systemic anti-HCC therapy prior to the resection surgery (except the resection surgery), such as liver transplantation, intervention, ablation, radiotherapy, chemotherapy, molecular targeted therapy or other anti-HCC therapy The subject took Sorafenib prior to randomization The subject took other study/investigational drugs 7 days prior to randomization The subject took Kang Laike injection/soft capsule，or Jinke Huaier granule 7 days prior to randomization The subject has central nervous system disease, mental illness, unstable angina, congestive heart failure, severe arrhythmia or other severe uncontrolled diseases The subject has history of investigational drug or similar drug allergy The baseline examination indicates that infection, bleeding, bile leakage, or other postoperative complications are present The subject is pregnant, lactating, or urine pregnancy test result is positive Baseline (post-resection) examination exist tumor recurrence or metastasis;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: the Tyroserleutide for injection<br>the Tyroserleutide for injection at the dosage of 6mg/d Gan Fu Le Tablets，6 tablets,po,tid | Drug: Gan Fu Le Tablets<br>* 6 Tablets，tid,po<br>Drug: Tyroserleutide for injection<br>* 6mg/d, 5days,ivgtt<br>|
| Placebo Comparator: the placebo group<br>the placebo Gan Fu Le Tablets，6 tablets,po,tid | Drug: Gan Fu Le Tablets<br>* 6 Tablets，tid,po<br>Drug: Placebo<br>* 0mg/d, 5days,ivgtt<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS （Overall Survival） | The time from randomization to death due to any reason | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RFS(Recurrence Free Survival) | The time from randomization to recurrence, metastasis or death due to any reason | 3 years |