Clinical trial NCT01489566: Study of Tyroserleutide for Injection in Hepatocellular Carcinoma (HCC) Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hepatocellular,Carcinoma
Keywords: Hepatocellular,Carcinoma,recurrence
Lead sponsor: Shenzhen Kangzhe Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
name: Medpace, Inc.
First posted: 2011-12-09
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: RFS(Recurrence Free Survival)
timeFrame: 0-2years
Secondary outcomes:
measure: OS （Overall Survival）
timeFrame: 0-2years
measure: QOL score
timeFrame: 0-2years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Tang ZhaoYou, Academician
role: STUDY_CHAIR
affiliation: Second Milliary Medical University,Eastern Hepatobiliary Surgery Hosipital
name: Wu Meng Chao, Academician
role: STUDY_CHAIR
affiliation: Shanghai Zhongshan Hospital
name: Fan Jia, professor
role: STUDY_DIRECTOR
affiliation: Second Milliary Medical University,Eastern Hepatobiliary Surgery Hosipital
name: Yang Jia Mei, professor
role: STUDY_DIRECTOR
affiliation: Shanghai Zhongshan Hospital
name: Sun Hui Chuan, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Milliary Medical University,Eastern Hepatobiliary Surgery Hosipital
name: Yan Yi Qun, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of College of Medicine, Zhejiang Universtiy
name: Zheng Shu Sen, Academician
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital Zhejiang University School of Medicine
name: Wu Yu Lian, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Dong Jia Hong, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking Union Medical College Hospital
name: Sang Xin Ting, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-sen University
name: Chen Min Shan, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-sen University
name: Guo Rong Ping, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Medical College,Huazhong University of Science and Technology Wuhan Union Hospital
name: Zheng Qi Chang, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hubei Cancer Hospital
name: Xia Xiao Qin, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Fujian Medical University
name: Liu Jing Feng, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Fujian Medical University Union Hospital
name: Chen Yan Ling, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Fujian Cancer Hospital
name: Ying Min Gang, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Cancer Hospital and Institute
name: Shi Xue Tao, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Provincial Hospital
name: Liu Jun, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Provincial Hospital
name: Liu Ji Yong, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Provincial People's Hospital
name: Wu Jin Shu, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xiangya Hospital of Central South University
name: Wang Zhi Ming, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sichuan Provincial People's Hospital
name: Yang Xun, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: West China Hospital,Sichuan Universtiy
name: Yan Lv Nan, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Southwest Hospital, China
name: Bie Ping, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Southwest Hospital, China
name: Ma Kuan Sheng, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Liu Qing Guang, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xijing Hospital
name: Han Ying, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Wang Xue Hao, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Ding Yi Tao, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Hao Xi Shan, Academician
role: PRINCIPAL_INVESTIGATOR
affiliation: Center of First Affiliated Hospital of Harbin Medical University
name: Liu Lian Xin, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Jilin University
name: Li Wei, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Jilin University
name: Wang Guang Yi, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Provincial People's Hospital
name: Jiang Bo, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital Zhejiang University School of Medicine
name: Du Qin, professor
role: PRINCIPAL_INVESTIGATOR
References: