<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/NCT01681446</url>
  </required_header>
  <id_info>
    <org_study_id>LCI IFNa miR-26</org_study_id>
    <nct_id>NCT01681446</nct_id>
  </id_info>
  <brief_title>Adjuvant IFN-α for Patients Underwent Curative Surgery for HCC With a Low miR-26 Expression</brief_title>
  <official_title>The Effect of Postoperative Interferon-alpha Treatment in Patients Underwent Curative Surgery for Hepatocellular Carcinoma With a Low miR-26 Expression: a Multi-center Randomized Clinical Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether interferon-alpha is effective in prevention&#xD;
      of tumor recurrence for the patients with a low miR-26 expression in tumor after curative&#xD;
      resection of hepatocellular carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND: Postoperative interferon-alpha (IFN-alpha) therapy improved survival in patients&#xD;
      with hepatocellular carcinoma (HCC). MiR-26 is a predictive marker for the effect of&#xD;
      postoperative interferon-alpha treatment in patients with HCC. Our study is to identify the&#xD;
      effect of postoperative IFN-alpha treatment in patients with a low miR-26 expression in tumor&#xD;
      after resection of HCC.&#xD;
&#xD;
      METHODS: A quantitative RT-PCR assays of miR-26 are performed on specimens which are&#xD;
      collected from patients who underwent a curative resection of HCC. These patients with low&#xD;
      miR-26 expression will return to the hospital 4 to 6 weeks after the resection following the&#xD;
      baseline examination to rule out residual tumor. If all requirements are satisfied, these&#xD;
      patients will be randomly assigned to the treatment group who received postoperative&#xD;
      IFN-alpha therapy or the control group who will not receive any anti-cancer treatment.&#xD;
      Disease-free survival, overall survival, time to recurrence and the side effects will be&#xD;
      observed.&#xD;
&#xD;
      Anticipated RESULTS: IFN-alpha treatment improved the disease-free survival in patients with&#xD;
      a low miR-26 expression in tumor after curative resection of HCC, probably by inhibiting&#xD;
      tumor recurrence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">August 2019</completion_date>
  <primary_completion_date type="Anticipated">August 2019</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>disease free survival</measure>
    <time_frame>5 years</time_frame>
    <description>interval between the dates of surgery and tumor recurrence or patient death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>interval between the dates of surgery and patient death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to recurrence</measure>
    <time_frame>5 years</time_frame>
    <description>interval between the dates of surgery and tumor recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events</measure>
    <time_frame>eighteen months</time_frame>
    <description>Number of Participants with Adverse Events（hypohepatia,fever,leukopenia and thrombopenia）will be measured</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">296</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>interferon-alpha (IFN-alpha)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>interferon-alpha is intramuscularly or subcutaneously injected at 30 μg three times a week or 50 μg twice a week for 18 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>no anti-cancer interventions were assigned</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>interferon-alpha (IFN-alpha)</intervention_name>
    <description>interferon-alpha is intramuscular injected 30 μg three times a week or 50 μg twice a week for 18 months</description>
    <arm_group_label>interferon-alpha (IFN-alpha)</arm_group_label>
    <other_name>Recombinant Human Interferon α1b for Injection</other_name>
    <other_name>SINOGEN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Perioperative Period Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent;&#xD;
&#xD;
          2. Aged ≥ 18 years and ≤ 75 years old, male or female；&#xD;
&#xD;
          3. Patients with a low miR-26 expression in tumor (confirmed by RT-PCR) underwent a&#xD;
             curative resection of HCC;&#xD;
&#xD;
          4. The tumor characteristics must meet the following:&#xD;
&#xD;
               1. tumor diameter is between 3 to 8 centimeters,and the number of tumor is less than&#xD;
                  3&#xD;
&#xD;
               2. no thrombosis is detected in the main branches of the portal vein, hepatic vein&#xD;
                  and bile duct by preoperative imaging or by intra-operative findings&#xD;
&#xD;
               3. no extrahepatic and lymph node metastasis&#xD;
&#xD;
        Perioperative Period Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant malignant primary tumor(s) in other systems is/are present;&#xD;
&#xD;
          2. The subject receives any previous systemic anti-HCC therapy prior to the resection&#xD;
             surgery, such as liver transplantation, intervention, ablation, radiotherapy,&#xD;
             chemotherapy, molecular targeted therapy or other anti-HCC therapy;&#xD;
&#xD;
          3. The subject takes other study/investigational drugs during this study;&#xD;
&#xD;
          4. The subject has cerebrovascular accident, renal insufficiency, depression,&#xD;
             hyperthyreosis, hypothyroidism or other severe uncontrolled diseases;&#xD;
&#xD;
          5. The subject has a history of study drug or similar drug allergy.&#xD;
&#xD;
        Baseline (Post-Surgery 4 to 6 weeks) Inclusion Criteria:&#xD;
&#xD;
          1. Baseline (post-resection) blood routine examination shows that the number of&#xD;
             leukocyte&gt;2.5*10^9/L and platelet count&gt;40*10^9/L;&#xD;
&#xD;
          2. Child-Pugh score of class A at baseline.&#xD;
&#xD;
        Baseline (Post-Surgery 4 to 6 weeks) Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant malignant primary tumor(s) in other systems is/are present;&#xD;
&#xD;
          2. The subject takes other study/investigational drugs within 4 weeks prior to&#xD;
             randomization;&#xD;
&#xD;
          3. The baseline examination indicates that infection, bleeding, bile leakage, or other&#xD;
             postoperative complications are present;&#xD;
&#xD;
          4. The baseline examination suggests the presence of tumor metastasis;&#xD;
&#xD;
          5. The subject has cerebrovascular accident, renal insufficiency, depression,&#xD;
             hyperthyreosis, hypothyroidism or other severe uncontrolled diseases;&#xD;
&#xD;
          6. The subject has a history of investigational drug or similar drug allergy;&#xD;
&#xD;
          7. The subject is pregnant, lactating, or urine pregnancy test result is positive.&#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>Jia Fan, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Xin Wei Wang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute, NIH, US</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mei-ling Li</last_name>
    <phone>64041990</phone>
    <phone_ext>2936</phone_ext>
    <email>livercongress@zs-hospital.sh.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Mengchao hepatobiliary hospital，Fujian Medical University，and Liver disease research center of Fujian province</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jingfeng Liu</last_name>
      <email>drjingfeng@yahoo.com.cn</email>
    </contact>
    <investigator>
      <last_name>Jingfeng Liu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital, Xiamen University</name>
      <address>
        <city>Xiamen</city>
        <state>Fujian</state>
        <zip>361004</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ping-Guo Liu, MD</last_name>
    </contact>
    <investigator>
      <last_name>Ping-Guo Liu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Liver Cancer Institute and Zhongshan Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mei-ling Li</last_name>
      <phone>64041990</phone>
      <phone_ext>2936</phone_ext>
      <email>livercongress@zs-hospital.sh.cn</email>
    </contact>
    <investigator>
      <last_name>Jia Fan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hui-Chuan Sun, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ShanghaiBio Coorperation</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jason Gang Jin, PhD</last_name>
      <phone>13818588366</phone>
      <email>jasongjin@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Jason Gang Jin, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Tumor Hospital, Tianjin Medical University</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ti Zhang, MD</last_name>
      <email>zhangti2001@yahoo.com.cn</email>
    </contact>
    <investigator>
      <last_name>Qiang Li, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ti Zhang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <reference>
    <citation>Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009 Oct 8;361(15):1437-47. doi: 10.1056/NEJMoa0901282.</citation>
    <PMID>19812400</PMID>
  </reference>
  <reference>
    <citation>Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006 Jul;132(7):458-65. doi: 10.1007/s00432-006-0091-y. Epub 2006 Mar 24.</citation>
    <PMID>16557381</PMID>
  </reference>
  <reference>
    <citation>Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, Fan ST, Wong J. A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg. 2007 Jun;245(6):831-42. doi: 10.1097/01.sla.0000245829.00977.45.</citation>
    <PMID>17522506</PMID>
  </reference>
  <reference>
    <citation>Clavien PA. Interferon: the magic bullet to prevent hepatocellular carcinoma recurrence after resection? Ann Surg. 2007 Jun;245(6):843-5. doi: 10.1097/SLA.0b013e31805d0788. No abstract available.</citation>
    <PMID>17522507</PMID>
  </reference>
  <reference>
    <citation>Qian YB, Zhang JB, Wu WZ, Fang HB, Jia WD, Zhuang PY, Zhang BH, Pan Q, Xu Y, Wang L, Tang ZY, Sun HC. P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer. 2006 Oct 1;107(7):1562-9. doi: 10.1002/cncr.22206.</citation>
    <PMID>16948122</PMID>
  </reference>
  <reference>
    <citation>Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q, Ye SL. High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology. 2000 Jul;32(1):43-8. doi: 10.1053/jhep.2000.8525.</citation>
    <PMID>10869287</PMID>
  </reference>
  <reference>
    <citation>Wang L, Wu WZ, Sun HC, Wu XF, Qin LX, Liu YK, Liu KD, Tang ZY. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg. 2003 Jul-Aug;7(5):587-94. doi: 10.1016/s1091-255x(03)00072-6.</citation>
    <PMID>12850669</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>May 30, 2018</last_update_submitted>
  <last_update_submitted_qc>May 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Jia Fan</investigator_full_name>
    <investigator_title>Professor of Surgery</investigator_title>
  </responsible_party>
  <keyword>hepatocellular carcinoma</keyword>
  <keyword>interferon-alpha</keyword>
  <keyword>miR-26</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Interferon-alpha</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/NCT01681446
org study id: LCI IFNa miR-26
nct id: NCT01681446
lead sponsor: 
has dmc: No
The purpose of the study is to determine whether interferon-alpha is effective in prevention
      of tumor recurrence for the patients with a low miR-26 expression in tumor after curative
      resection of hepatocellular carcinoma.
BACKGROUND: Postoperative interferon-alpha (IFN-alpha) therapy improved survival in patients
      with hepatocellular carcinoma (HCC). MiR-26 is a predictive marker for the effect of
      postoperative interferon-alpha treatment in patients with HCC. Our study is to identify the
      effect of postoperative IFN-alpha treatment in patients with a low miR-26 expression in tumor
      after resection of HCC.

      METHODS: A quantitative RT-PCR assays of miR-26 are performed on specimens which are
      collected from patients who underwent a curative resection of HCC. These patients with low
      miR-26 expression will return to the hospital 4 to 6 weeks after the resection following the
      baseline examination to rule out residual tumor. If all requirements are satisfied, these
      patients will be randomly assigned to the treatment group who received postoperative
      IFN-alpha therapy or the control group who will not receive any anti-cancer treatment.
      Disease-free survival, overall survival, time to recurrence and the side effects will be
      observed.

      Anticipated RESULTS: IFN-alpha treatment improved the disease-free survival in patients with
      a low miR-26 expression in tumor after curative resection of HCC, probably by inhibiting
      tumor recurrence.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: disease free survival
time frame: 5 years
description: interval between the dates of surgery and tumor recurrence or patient death
measure: overall survival
time frame: 5 years
description: interval between the dates of surgery and patient death
measure: time to recurrence
time frame: 5 years
description: interval between the dates of surgery and tumor recurrence
measure: Number of Participants with Adverse Events
time frame: eighteen months
description: Number of Participants with Adverse Events（hypohepatia,fever,leukopenia and thrombopenia）will be measured
arm group label: interferon-alpha (IFN-alpha)
arm group type: Active Comparator
description: interferon-alpha is intramuscularly or subcutaneously injected at 30 μg three times a week or 50 μg twice a week for 18 months
arm group label: control
arm group type: No Intervention
description: no anti-cancer interventions were assigned
intervention type: Drug
intervention name: interferon-alpha (IFN-alpha)
description: interferon-alpha is intramuscular injected 30 μg three times a week or 50 μg twice a week for 18 months
arm group label: interferon-alpha (IFN-alpha)
other name: Recombinant Human Interferon α1b for Injection
other name: SINOGEN
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jia Fan, MD, PHD
role: Principal Investigator
affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
last name: Xin Wei Wang, PhD
role: Principal Investigator
affiliation: National Cancer Institute, NIH, US
last name: Mei-ling Li
phone: 64041990
phone ext: 2936
email: livercongress@zs-hospital.sh.cn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
country: United States
citation: Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009 Oct 8;361(15):1437-47. doi: 10.1056/NEJMoa0901282.
PMID: 19812400
citation: Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006 Jul;132(7):458-65. doi: 10.1007/s00432-006-0091-y. Epub 2006 Mar 24.
PMID: 16557381
citation: Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, Fan ST, Wong J. A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg. 2007 Jun;245(6):831-42. doi: 10.1097/01.sla.0000245829.00977.45.
PMID: 17522506
citation: Clavien PA. Interferon: the magic bullet to prevent hepatocellular carcinoma recurrence after resection? Ann Surg. 2007 Jun;245(6):843-5. doi: 10.1097/SLA.0b013e31805d0788. No abstract available.
PMID: 17522507
citation: Qian YB, Zhang JB, Wu WZ, Fang HB, Jia WD, Zhuang PY, Zhang BH, Pan Q, Xu Y, Wang L, Tang ZY, Sun HC. P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer. 2006 Oct 1;107(7):1562-9. doi: 10.1002/cncr.22206.
PMID: 16948122
citation: Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q, Ye SL. High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology. 2000 Jul;32(1):43-8. doi: 10.1053/jhep.2000.8525.
PMID: 10869287
citation: Wang L, Wu WZ, Sun HC, Wu XF, Qin LX, Liu YK, Liu KD, Tang ZY. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg. 2003 Jul-Aug;7(5):587-94. doi: 10.1016/s1091-255x(03)00072-6.
PMID: 12850669
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Jia Fan
investigator title: Professor of Surgery
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Interferons
mesh term: Interferon-alpha