Study of Tyroserleutide for Injection in Hepatocellular Carcinoma (HCC) Patients
A Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Phase III Clinical Trial to Evaluate the Safety and Efficacy of Injectable Tyroserleutide to Treat Hepatocellular Carcinoma
Lead SponsorShenzhen Kangzhe Pharmaceutical Co., Ltd.
This is a randomized, double-blinded, placebo-controlled, multi-center Clinical Trial. Patients with no tumor lesions one month 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.
The objective is to evaluate the effect of Injectable Tyroserleutide on the recurrence-free survival,overall survival,quality of life,and the safety and tolerability of subjects after the resection of hepatocellular carcinoma
Subjects will return to the hospital 25±5 days after the resection of hepatocellular carcinoma following the baseline examination. Baseline imaging data will be sent to the lead study site imaging center for review and verification. The investigator will determine whether the subject satisfies all inclusion/exclusion criteria. If all requirements are satisfied, then randomization will occur 25±5 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). The Investigator will administer chemotherapy according to the subject's condition. On the next day, experimental drug therapy will begin, and the relevant laboratory tests will be performed within 3 days after the end the study drug infusion.
Cycles will occur every four weeks for the first 6 cycles (i.e. cycles 2, 3, 4, 5, and 6 will begin on days 28 ± 3, 56 ± 3, 84 ± 3, 112 ± 3, and 140 ± 3, respectively). The second 6 cycles will occur every eight weeks (i.e. cycles 7, 8, 9, 10, and 11, will begin on days 196 ± 3, 252 ± 3, 308 ± 3, 364 ± 3, and 420 ± 3, respectively).
the participant will receive medical inspection so as to observe and ensure drug safety.
A CT scan will be performed for each participant to exclude the recurrence or metastasis of tumor and assess the effects of treatment once before the initiation of each new cycle.
mitomycin(10mg)+Fluorouracil(1.0g),through the chemoradiative pump,every cycle,5-30 minites; Tyroserleutide for injection(30mg) ,through the micro infusion pump,every cycle,3-5 days
mitomycin(10mg)+Fluorouracil(1.0g),through the chemoradiative pump,every cycle,5-30 minites; the placebo(30mg) ,through the micro infusion pump,every cycle,3-5 days
the Tyroserleutide for injection at the dosage of 6mg/d
Perioperative Period Inclusion Criteria Signed informed consent; Aged ≥ 18 years and ≤ 75 years old, male or female； Subject underwent a complete resection of hepatocellular carcinoma (confirmed by pathology); The tumor characteristics must meet one of the following: Tumor thrombosis in the portal vein branches is detected by either; Preoperative imaging, or; Intraoperative visual observation. Tumor thrombosis in the portal vein branches was not detected; and A single tumor with a maximum diameter ≥8cm confirmed by preoperative imaging, and histological evidence of micro vascular tumor thrombosis; or Preoperative imaging confirmed that there are 2 or more tumor lesions Perioperative Period Exclusion Criteria Concomitant malignant primary tumor(s) in other systems is/are present; Tumor thrombosis in the main 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 other study/investigational drugs 7 days prior to the resection surgery; 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 study drug or similar drug allergy Baseline (Post-SurgeryDay 25 ± 5) Inclusion Criteria Baseline (post-resection) liver CT (normal CT + contrast enhanced CT) and chest CT scan show no tumor lesions; Child-Pugh score of class A at baseline Baseline (Post-SurgeryDay 25 ± 5) Exclusion Criteria Body surface area is < 1.47 m2 or > 1.92 m2; Concomitant malignant primary tumor(s) in other systems is/are present; The subject took other study/investigational drugs within 4 weeks prior to randomization; The baseline examination indicates that infection, bleeding, bile leakage, or other postoperative complications are present; The baseline examination suggests the presence of tumor metastasis; 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 subject is pregnant, lactating, or urine pregnancy test result is positive