the Efficacy and Safety of Ginsenoside Rg3 Capsule in Prevention of Postoperative Recurrence of Hepatocellular Carcinoma

Stage I Hepatocellular Carcinoma Clinical Trial

— Rg3  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01717066
• Other study ID #: EHBH-RCT-2011-002
• Status: Completed
• Phase: N/A
• First received: October 26, 2012
• Last updated: March 30, 2016
• Start date: April 2012
• Est. completion date: May 2015

Study information

• Verified date: March 2016
• Source: Eastern Hepatobiliary Surgery Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 480
• Est. completion date: May 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Stage I Hepatocellular Carcinoma
• Stage II Hepatocellular Carcinoma

Intervention

Drug:
• the ginsenoside Rg3

• Placebo

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Tumor Hospital,Sun Yat-san University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Zhongshan hospital,Fudan University	Shanghai
China	Tongji Hospital,Huazhong University of Science & Technology	Wuhan	Hubei

Sponsors (6)

Lead Sponsor	Collaborator
ShenFeng	First Affiliated Hospital of Fujian Medical University, First Affiliated Hospital of Harbin Medical University, Huazhong University of Science and Technology, Shanghai Zhongshan Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (8)

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. — View 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. — View 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. — View 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. — View 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. — View 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. Epub 2006 May 12. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	side effect	the adverse reactions of the application of ginsenoside Rg3,for example:severe dry pharynx	eighteen months	Yes
Primary	time to recurrence	the interval between the initial hepatectomy and date of diagnosis of recurrent HCC	1,2,3 years	No
Secondary	overall survival	the interval between the date of the initial hepatectomy and the date of death or last follow-up	1,2,3 years	Yes