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

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

Study Overview

• Status: Unknown
• Conditions: Hepatocellular,Carcinoma
• Intervention / Treatment: Drug: Tyroserleutide for injection ,chemotherapy(mitomycin, and Fluorouracil ); Drug: the placebo ,chemotherapy(mitomycin, and Fluorouracil )

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Zhongshan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Perioperative Period Inclusion Criteria

1. Signed informed consent;
2. Aged ≥ 18 years and ≤ 75 years old, male or female；
3. Subject underwent a complete resection of hepatocellular carcinoma (confirmed by pathology);

4. 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

1. Concomitant malignant primary tumor(s) in other systems is/are present;
2. Tumor thrombosis in the main branch of portal vein or in hepatic vein is detected by preoperative imaging or observed during the surgery;
3. 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;
4. The subject took other study/investigational drugs 7 days prior to the resection surgery;
5. The subject has central nervous system disease, mental illness, unstable angina, congestive heart failure, severe arrhythmia or other severe uncontrolled diseases;
6. The subject has history of study drug or similar drug allergy

Baseline (Post-SurgeryDay 25 ± 5) Inclusion Criteria

1. Baseline (post-resection) liver CT (normal CT + contrast enhanced CT) and chest CT scan show no tumor lesions;
2. Child-Pugh score of class A at baseline

Baseline (Post-SurgeryDay 25 ± 5) Exclusion Criteria

1. Body surface area is < 1.47 m2 or > 1.92 m2;
2. Concomitant malignant primary tumor(s) in other systems is/are present;
3. The subject took other study/investigational drugs within 4 weeks prior to randomization;
4. The baseline examination indicates that infection, bleeding, bile leakage, or other postoperative complications are present;
5. The baseline examination suggests the presence of tumor metastasis;
6. The subject has central nervous system disease, mental illness, unstable angina, congestive heart failure, severe arrhythmia or other severe uncontrolled diseases;
7. The subject has history of investigational drug or similar drug allergy;
8. The subject is pregnant, lactating, or urine pregnancy test result is positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tyroserleutide for injection; the Tyroserleutide for injection at the dosage of 6mg/d	Drug: Tyroserleutide for injection ,chemotherapy(mitomycin, and Fluorouracil ); 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
Placebo Comparator: the placebo	Drug: the placebo ,chemotherapy(mitomycin, and Fluorouracil ); 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

What is the study measuring?

Primary 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	0-2years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS （Overall Survival）	The time from randomization to death due to any reason	0-2years
QOL score	Quality of life score	0-2years

Collaborators and Investigators

• Sponsor: Shenzhen Kangzhe Pharmaceutical Co., Ltd.
• Collaborators: Fudan University; Medpace, Inc.
• Investigators: Study Chair: Tang ZhaoYou, Academician, Shanghai Zhongshan Hospital; Study Chair: Wu Meng Chao, Academician, Second Milliary Medical University,Eastern Hepatobiliary Surgery Hosipital; Study Director: Fan Jia, professor, Shanghai Zhongshan Hospital; Study Director: Yang Jia Mei, professor, Second Milliary Medical University,Eastern Hepatobiliary Surgery Hosipital; Principal Investigator: Sun Hui Chuan, professor, Shanghai Zhongshan Hospital; Principal Investigator: Yan Yi Qun, professor, Second Milliary Medical University,Eastern Hepatobiliary Surgery Hosipital; Principal Investigator: Zheng Shu Sen, Academician, The First Affiliated Hospital of College of Medicine, Zhejiang Universtiy; Principal Investigator: Wu Yu Lian, professor, Second Affiliated Hospital Zhejiang University School of Medicine; Principal Investigator: Dong Jia Hong, professor, Chinese PLA General Hospital; Principal Investigator: Sang Xin Ting, professor, Peking Union Medical College Hospital; Principal Investigator: Chen Min Shan, professor, Sun Yat-sen University; Principal Investigator: Guo Rong Ping, professor, Sun Yat-sen University; Principal Investigator: Zheng Qi Chang, professor, Tongji Medical College,Huazhong University of Science and Technology Wuhan Union Hospital; Principal Investigator: Xia Xiao Qin, professor, Hubei Cancer Hospital; Principal Investigator: Liu Jing Feng, professor, First Affiliated Hospital of Fujian Medical University; Principal Investigator: Chen Yan Ling, professor, Fujian Medical University Union Hospital; Principal Investigator: Ying Min Gang, professor, Fujian Cancer Hospital; Principal Investigator: Shi Xue Tao, professor, Shandong Provincial Cancer Hospital; Principal Investigator: Liu Jun, professor, Shandong Provincial Hospital; Principal Investigator: Liu Ji Yong, professor, Shandong Provincial Hospital; Principal Investigator: Wu Jin Shu, professor, Hunan Provincial People's Hospital; Principal Investigator: Wang Zhi Ming, professor, Xiangya Hospital of Central South University; Principal Investigator: Yang Xun, professor, Sichuan Provincial People's Hospital; Principal Investigator: Yan Lv Nan, professor, West China Hospital,Sichuan Universtiy; Principal Investigator: Bie Ping, professor, Southwest Hospital, China; Principal Investigator: Ma Kuan Sheng, professor, Southwest Hospital, China; Principal Investigator: Liu Qing Guang, professor, First Affiliated Hospital Xi'an Jiaotong University; Principal Investigator: Han Ying, professor, Xijing Hospital; Principal Investigator: Wang Xue Hao, professor, The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Ding Yi Tao, professor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Principal Investigator: Hao Xi Shan, Academician, Tianjin Medical University Cancer Institute and Hospital; Principal Investigator: Liu Lian Xin, professor, Center of First Affiliated Hospital of Harbin Medical University; Principal Investigator: Li Wei, professor, The first Affiliated Hospital of Jilin University; Principal Investigator: Wang Guang Yi, professor, The first Affiliated Hospital of Jilin University; Principal Investigator: Jiang Bo, professor, Hunan Provincial People's Hospital; Principal Investigator: Du Qin, professor, Second Affiliated Hospital Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): March 1, 2013
• Study Completion (Anticipated): August 1, 2013

Study Registration Dates

• First Submitted: December 1, 2011
• First Submitted That Met QC Criteria: December 8, 2011
• First Posted (Estimate): December 9, 2011

Study Record Updates

• Last Update Posted (Estimate): December 14, 2011
• Last Update Submitted That Met QC Criteria: December 13, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Hepatocellular,Carcinoma,recurrence
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Alkylating Agents; Antibiotics, Antineoplastic; Fluorouracil; Mitomycins; Mitomycin
• Other Study ID Numbers: TYS-CN-1.1PUMP III