Clinical trial NCT01717066: the Efficacy and Safety of Ginsenoside Rg3 Capsule in Prevention of Postoperative Recurrence of Hepatocellular Carcinoma
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Clinical Study to Evaluate the Efficacy and Safety of Ginsenoside Rg3 Capsule in Prevention of Postoperative Recurrence of Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stage I Hepatocellular Carcinoma
Stage II Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
ginsenoside Rg3
Lead sponsor: Eastern Hepatobiliary Surgery Hospital
Sponsor class: OTHER
Collaborators: name: Huazhong University of Science and Technology
name: Shanghai Zhongshan Hospital
name: Sun Yat-sen University
name: First Affiliated Hospital of Harbin Medical University
name: First Affiliated Hospital of Fujian Medical University
First posted: 2012-10-30
Enrollment: 480
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: PREVENTION

Brief summary: Using the subject with hepatocellular carcinoma in the conventional therapy to evaluate the efficacy and safety of ginsenoside Rg3 (20mg BID) and placebo in prevention and treatment of postoperative recurrence of liver cancer,respectively

Detailed description: 1. Randomized, double-blind, multi-center, placebo-controlled, parallel-group;
2. Subject population: patients undergone radical resection of hepatocellular carcinoma;
3. Active drug group:

Ginsenoside Rg3 group: general treatment + ginsenoside Rg3 Control group (placebo group): general treatment + placebo 4.Method of group assignment: 5research centers, central-block-stratified randomization, a ratio of active drug group to control group: 2:1 5.Dose and mode of administration: Ginsenoside Rg3 group: ginsenoside Rg3 20mg BID, two months as one cycle, continue until recurrence occurs Placebo Group: placebo, 2 capsules, BID, continue until recurrence occurs 6.Study period: Screening phase: screening for enrollment within 8 weeks after the radical resection Follow up: review every 2-3 months following the surgery Post-trial investigation: within 28 days after the trial is ended or the recurrence occurs

Eligibility criteria: Inclusion Criteria:

* 18-75 years old,male and female
* Mainly based on the criteria for liver cancer TNM stage I and II (edition 7) and BCLC stage A, the following needs to be satisfied:

  1. individual tumor larger than or equal to 2 cm and smaller than or equal to 10 cm in the maximum diameter
  2. multiple tumors with no more than three tumors
  3. No macroscopic tumor embolus
* ECOG performance state is 0-1
* Child-Pugh grade is A
* The clinical review confirms the absence of recurrence within 8 weeks before the enrollment
* Sign the informed consent

Exclusion Criteria:

* Pregnant and breast-feeding women
* Patients with severe diseases in the brain, heart,lungs, kidneys and hematological system
* Patients who have received other anti-tumor therapies before the surgery (including liver transplantation, TACE, local tumor ablation, chemotherapy, radiotherapy, molecular targeted therapy and other anti-tumor therapy)
* DDS chemotherapy pump placed in the portal vein during the surgery
* Patients who are participating in other drug trials
* Patients known or suspected to be allergic to ginsenoside, with a history of allergy to biological preparations, allergic constitution or currently in an allergic state;
* With active severe clinical infection
* Epilepsy episode which needs drug therapy
* With a history of allotransplantation;
* With a previous history of tumor in other systems, but except for:

  1. Carcinoma in situ of cervix
  2. Basal cell carcinoma after treatment,Superficial bladder cancer (Ta, Tis and T1
  3. Any cancer after curative treatment no less than three years ago
* Patients with signs or a history of bleeding diathesis
* Patients currently receiving kidney dialysis
* A history of bleeding in the gastrointestinal tract within 30 days, or severe gastroesophageal varices with red signs; with a history of gastroesophageal variceal hemorrhage
* Recurrent HCC
* Patients unable to take drug orally
* Patients inappropriate to participate in the trial upon the investigator's judgment

Primary outcomes:
measure: time to recurrence
timeFrame: 1,2,3 years
Secondary outcomes:
measure: overall survival
timeFrame: 1,2,3 years
Other outcomes:
measure: side effect
timeFrame: eighteen months
Locations:
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Tumor Hospital,Sun Yat-san University
state: Guangdong
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Wuhan
country: China
facility: Tongji Hospital,Huazhong University of Science ＆ Technology
state: Hubei
city: Shanghai
country: China
facility: Zhongshan hospital,Fudan University
Study officials:
affiliation: Eastern Hepatobiliary Surgery Hospital
name: Feng Shen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yue PY, Wong DY, Wu PK, Leung PY, Mak NK, Yeung HW, Liu L, Cai Z, Jiang ZH, Fan TP, Wong RN. The angiosuppressive effects of 20(R)- ginsenoside Rg3. Biochem Pharmacol. 2006 Aug 14;72(4):437-45. doi: 10.1016/j.bcp.2006.04.034. Epub 2006 May 12.
citation: Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL, Song HB, Yi C. Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. BMC Cancer. 2009 Jul 23;9:250. doi: 10.1186/1471-2407-9-250.
citation: Zhang Q, Kang X, Yang B, Wang J, Yang F. Antiangiogenic effect of capecitabine combined with ginsenoside Rg3 on breast cancer in mice. Cancer Biother Radiopharm. 2008 Oct;23(5):647-53. doi: 10.1089/cbr.2008.0532.
citation: Xu TM, Cui MH, Xin Y, Gu LP, Jiang X, Su MM, Wang DD, Wang WJ. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis. Chin Med J (Engl). 2008 Aug 5;121(15):1394-7.
citation: Iishi H, Tatsuta M, Baba M, Uehara H, Nakaizumi A, Shinkai K, Akedo H, Funai H, Ishiguro S, Kitagawa I. Inhibition by ginsenoside Rg3 of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats. Clin Exp Metastasis. 1997 Nov;15(6):603-11. doi: 10.1023/a:1018491314066.
citation: Lee JY, Jung KH, Morgan MJ, Kang YR, Lee HS, Koo GB, Hong SS, Kwon SW, Kim YS. Sensitization of TRAIL-induced cell death by 20(S)-ginsenoside Rg3 via CHOP-mediated DR5 upregulation in human hepatocellular carcinoma cells. Mol Cancer Ther. 2013 Mar;12(3):274-85. doi: 10.1158/1535-7163.MCT-12-0054. Epub 2012 Oct 10.
citation: Zhang C, Liu L, Yu Y, Chen B, Tang C, Li X. Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells. Mol Med Rep. 2012 May;5(5):1295-8. doi: 10.3892/mmr.2012.808. Epub 2012 Feb 23.
citation: Park HM, Kim SJ, Kim JS, Kang HS. Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways. Food Chem Toxicol. 2012 Aug;50(8):2736-41. doi: 10.1016/j.fct.2012.05.027. Epub 2012 May 22.