<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01717066</url>
  </required_header>
  <id_info>
    <org_study_id>EHBH-RCT-2011-002</org_study_id>
    <nct_id>NCT01717066</nct_id>
  </id_info>
  <brief_title>the Efficacy and Safety of Ginsenoside Rg3 Capsule in Prevention of Postoperative Recurrence of Hepatocellular Carcinoma</brief_title>
  <acronym>Rg3</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ShenFeng</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Huazhong University of Science and Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai Zhongshan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Harbin Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Fujian Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Eastern Hepatobiliary Surgery Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Using the subject with hepatocellular carcinoma in the conventional therapy to evaluate the&#xD;
      efficacy and safety of ginsenoside Rg3 (20mg BID) and placebo in prevention and treatment of&#xD;
      postoperative recurrence of liver cancer,respectively&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Randomized, double-blind, multi-center, placebo-controlled, parallel-group;&#xD;
&#xD;
        2. Subject population: patients undergone radical resection of hepatocellular carcinoma;&#xD;
&#xD;
        3. Active drug group:&#xD;
&#xD;
      Ginsenoside Rg3 group: general treatment + ginsenoside Rg3 Control group (placebo group):&#xD;
      general treatment + placebo 4.Method of group assignment: 5research centers,&#xD;
      central-block-stratified randomization, a ratio of active drug group to control group: 2:1&#xD;
      5.Dose and mode of administration: Ginsenoside Rg3 group: ginsenoside Rg3 20mg BID, two&#xD;
      months as one cycle, continue until recurrence occurs Placebo Group: placebo, 2 capsules,&#xD;
      BID, continue until recurrence occurs 6.Study period: Screening phase: screening for&#xD;
      enrollment within 8 weeks after the radical resection Follow up: review every 2-3 months&#xD;
      following the surgery Post-trial investigation: within 28 days after the trial is ended or&#xD;
      the recurrence occurs&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2012</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>time to recurrence</measure>
    <time_frame>1,2,3 years</time_frame>
    <description>the interval between the initial hepatectomy and date of diagnosis of recurrent HCC</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>1,2,3 years</time_frame>
    <description>the interval between the date of the initial hepatectomy and the date of death or last follow-up</description>
  </secondary_outcome>
  <other_outcome>
    <measure>side effect</measure>
    <time_frame>eighteen months</time_frame>
    <description>the adverse reactions of the application of ginsenoside Rg3,for example:severe dry pharynx</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">480</enrollment>
  <condition>Stage I Hepatocellular Carcinoma</condition>
  <condition>Stage II Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>the ginsenoside Rg3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>320 HCCs,the ginsenoside Rg3 capsule,4-8 weeks after surgery, will be taken, 2 capsules, BID, 8 weeks as one cycle, continue taking it until the tumor recurs or until the end date of the study for patients without recurrence</description>
  </arm_group>
  <arm_group>
    <arm_group_label>the placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>160 HCCs as control group with patients who don't receive any adjuvant therapy after liver resection, to compare with the treatment group</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>the ginsenoside Rg3</intervention_name>
    <arm_group_label>the ginsenoside Rg3</arm_group_label>
    <other_name>Shen Yi capsule</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>the placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-75 years old,male and female&#xD;
&#xD;
          -  Mainly based on the criteria for liver cancer TNM stage I and II (edition 7) and BCLC&#xD;
             stage A, the following needs to be satisfied:&#xD;
&#xD;
               1. individual tumor larger than or equal to 2 cm and smaller than or equal to 10 cm&#xD;
                  in the maximum diameter&#xD;
&#xD;
               2. multiple tumors with no more than three tumors&#xD;
&#xD;
               3. No macroscopic tumor embolus&#xD;
&#xD;
          -  ECOG performance state is 0-1&#xD;
&#xD;
          -  Child-Pugh grade is A&#xD;
&#xD;
          -  The clinical review confirms the absence of recurrence within 8 weeks before the&#xD;
             enrollment&#xD;
&#xD;
          -  Sign the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and breast-feeding women&#xD;
&#xD;
          -  Patients with severe diseases in the brain, heart,lungs, kidneys and hematological&#xD;
             system&#xD;
&#xD;
          -  Patients who have received other anti-tumor therapies before the surgery (including&#xD;
             liver transplantation, TACE, local tumor ablation, chemotherapy, radiotherapy,&#xD;
             molecular targeted therapy and other anti-tumor therapy)&#xD;
&#xD;
          -  DDS chemotherapy pump placed in the portal vein during the surgery&#xD;
&#xD;
          -  Patients who are participating in other drug trials&#xD;
&#xD;
          -  Patients known or suspected to be allergic to ginsenoside, with a history of allergy&#xD;
             to biological preparations, allergic constitution or currently in an allergic state;&#xD;
&#xD;
          -  With active severe clinical infection&#xD;
&#xD;
          -  Epilepsy episode which needs drug therapy&#xD;
&#xD;
          -  With a history of allotransplantation;&#xD;
&#xD;
          -  With a previous history of tumor in other systems, but except for:&#xD;
&#xD;
               1. Carcinoma in situ of cervix&#xD;
&#xD;
               2. Basal cell carcinoma after treatment,Superficial bladder cancer (Ta, Tis and T1&#xD;
&#xD;
               3. Any cancer after curative treatment no less than three years ago&#xD;
&#xD;
          -  Patients with signs or a history of bleeding diathesis&#xD;
&#xD;
          -  Patients currently receiving kidney dialysis&#xD;
&#xD;
          -  A history of bleeding in the gastrointestinal tract within 30 days, or severe&#xD;
             gastroesophageal varices with red signs; with a history of gastroesophageal variceal&#xD;
             hemorrhage&#xD;
&#xD;
          -  Recurrent HCC&#xD;
&#xD;
          -  Patients unable to take drug orally&#xD;
&#xD;
          -  Patients inappropriate to participate in the trial upon the investigator's judgment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Feng Shen, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Eastern Hepatobiliary Surgery Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Fujian Medical University</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350005</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tumor Hospital,Sun Yat-san University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tongji Hospital,Huazhong University of Science ＆ Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan hospital,Fudan University</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <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>
    <PMID>16793023</PMID>
  </reference>
  <reference>
    <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>
    <PMID>19624862</PMID>
  </reference>
  <reference>
    <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>
    <PMID>18999937</PMID>
  </reference>
  <reference>
    <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>
    <PMID>18959116</PMID>
  </reference>
  <reference>
    <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>
    <PMID>9344044</PMID>
  </reference>
  <reference>
    <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>
    <PMID>23053497</PMID>
  </reference>
  <reference>
    <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>
    <PMID>22366885</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>22634290</PMID>
  </reference>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>March 30, 2016</last_update_submitted>
  <last_update_submitted_qc>March 30, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 31, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Eastern Hepatobiliary Surgery Hospital</investigator_affiliation>
    <investigator_full_name>ShenFeng</investigator_full_name>
    <investigator_title>vice president of the Eastern Hepatobiliary Surgery Hospital</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>ginsenoside Rg3</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ginsenoside Rg3</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01717066
org study id: EHBH-RCT-2011-002
nct id: NCT01717066
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: time to recurrence
time frame: 1,2,3 years
description: the interval between the initial hepatectomy and date of diagnosis of recurrent HCC
measure: overall survival
time frame: 1,2,3 years
description: the interval between the date of the initial hepatectomy and the date of death or last follow-up
measure: side effect
time frame: eighteen months
description: the adverse reactions of the application of ginsenoside Rg3,for example:severe dry pharynx
arm group label: the ginsenoside Rg3
arm group type: Experimental
description: 320 HCCs,the ginsenoside Rg3 capsule,4-8 weeks after surgery, will be taken, 2 capsules, BID, 8 weeks as one cycle, continue taking it until the tumor recurs or until the end date of the study for patients without recurrence
arm group label: the placebo
arm group type: Placebo Comparator
description: 160 HCCs as control group with patients who don't receive any adjuvant therapy after liver resection, to compare with the treatment group
intervention type: Drug
intervention name: the ginsenoside Rg3
arm group label: the ginsenoside Rg3
other name: Shen Yi capsule
intervention type: Drug
intervention name: Placebo
arm group label: the placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Feng Shen, MD,PhD
role: Principal Investigator
affiliation: Eastern Hepatobiliary Surgery Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
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.
PMID: 16793023
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.
PMID: 19624862
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.
PMID: 18999937
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.
PMID: 18959116
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.
PMID: 9344044
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.
PMID: 23053497
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.
PMID: 22366885
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.
PMID: 22634290
responsible party type: Sponsor-Investigator
investigator affiliation: Eastern Hepatobiliary Surgery Hospital
investigator full name: ShenFeng
investigator title: vice president of the Eastern Hepatobiliary Surgery Hospital
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Recurrence
mesh term: Ginsenoside Rg3