<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/NCT03253250</url>
  </required_header>
  <id_info>
    <org_study_id>PEG-HCC</org_study_id>
    <nct_id>NCT03253250</nct_id>
  </id_info>
  <brief_title>The Investigation of Peginterferon Alfa-2a on the RFS of the Subjects With HCC Who Have Been Treated by Resection</brief_title>
  <official_title>A Prospective, Randomized, Multicenter, Open-label, Exploratory Study of Utilizing of Peginterferon Alfa-2a on the Relapse Rate of the Subjects With Hepatocellular Carcinoma Who Have Been Treated by Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Huashan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Huashan Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current study is a prospective, randomized, open, multi-center investigation. The aim of&#xD;
      current study is to investigate whether the Recurrence-free Survival Rate (RFS）of the&#xD;
      hepatitis B related -hepatocellular carcinoma subjects who have been treated by resection can&#xD;
      be improved by peginterferon alfa-2a&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The subjects who have been treated by resection due to hepatocellular carcinoma (HCC) will be&#xD;
      randomized into 2 groups: the subjects in group A will be treated by Nucleotide analogues&#xD;
      (NAs)( ETV, 0.5mg，qd；tenofovir disoproxil fumarate(TDF)，300mg，qd；ADV，10mg，qd）for 96 weeks;&#xD;
      the subjects in group B will be treated by peginterferon alfa-2a （135μg/week）combination with&#xD;
      NAs (ETV\TDF\ADV)for 96 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</primary_completion_date>
  <phase>Phase 4</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>Recurrence-free Survival Rate (RFS）</measure>
    <time_frame>2 years</time_frame>
    <description>Number of subjects without Recurrence in the total subjects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free Survival Rate (RFS）</measure>
    <time_frame>1 year</time_frame>
    <description>Number of subjects without Recurrence in the total subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate (OS）</measure>
    <time_frame>2 years</time_frame>
    <description>Number of subjects with survival in the total subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate (OS）</measure>
    <time_frame>1 year</time_frame>
    <description>Number of subjects with survival in the total subjects</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">432</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <condition>Hepatic Carcinoma</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The subjects will be treated by NAs (ETV, 0.5mg，qd；TDF，300mg，qd；ADV，10mg，qd）for 96 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will be treated by peginterferon alfa-2a （135μg/week）combination with NAs(ETV\TDF\ADV) for 96 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ETV；TDF；ADV</intervention_name>
    <description>NAs</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <other_name>entecavir;tenofovir disoproxil fumarate;adefovir</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Peginterferon Alfa-2a</intervention_name>
    <description>peginterferon</description>
    <arm_group_label>Group B</arm_group_label>
    <other_name>pegasys</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients with age ≥18 and ≤70 years;&#xD;
&#xD;
          2. Expected survival time &gt;3 months;&#xD;
&#xD;
          3. There should be evidences that chronic hepatitis B or hepatitis have been positive,&#xD;
             hepatitis B virus (HBV) DNA detectable or undetectable, Alanine&#xD;
             aminotransferase(ALT)&lt;upper limit of normal (ULN) or ≥ULN；&#xD;
&#xD;
          4. The patients have been treated by resection due to HCC;&#xD;
&#xD;
          5. The characteristic of tumor should be:Barcelona Clinic Liver Cancer(BCLC): 0,A,B&#xD;
&#xD;
          6. Child-Pugh scores:A&#xD;
&#xD;
          7. Agree to participate in the study and sign the patient informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients that have been treated by live&#xD;
             transplantation、chemoembolization、radiotherapy、chemotherapy、molecular targeted therapy&#xD;
             and biotherapy before the resection;&#xD;
&#xD;
          2. Patients that are treated by hepatotoxicity drugs 、immunosuppressant or adjuvant&#xD;
             chemotherapy after the resection;&#xD;
&#xD;
          3. Patients who be treated by transcatheter arterial chemoembolization(TACE) after&#xD;
             resection;&#xD;
&#xD;
          4. BCLC(Barcelona Clinic Liver Cancer):C、D before the resection;&#xD;
&#xD;
          5. History or other evidence of malignant tumor: except by basal cell carcinoma or&#xD;
             squamous cell carcinoma which are cured 、carcinoma in situs of cervix&#xD;
&#xD;
          6. Allergic history to interferon;&#xD;
&#xD;
          7. Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human&#xD;
             immunodeficiency virus (HIV);&#xD;
&#xD;
          8. History or other evidence of a medical condition associated with chronic liver disease&#xD;
             other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic&#xD;
             liver disease, alcoholic liver disease, toxin exposures, thalassemia);&#xD;
&#xD;
          9. absolute neutrophil count(ANC)&lt;1.5x 10^9/L or platelet count(PLT)&lt;70x 10^9/L&#xD;
&#xD;
         10. Creatinine over upper limit of normal;&#xD;
&#xD;
         11. History of severe psychiatric disease, especially depression. Severe psychiatric&#xD;
             disease is defined as major depression or psychosis that treated with antidepressant&#xD;
             medication or a major tranquilizer at therapeutic doses respectively at any time prior&#xD;
             to 3 months or any history of the following: a suicidal attempt hospitalization for&#xD;
             psychiatric disease, or a period of disability due to a psychiatric disease;&#xD;
&#xD;
         12. History of severe cardiac disease (e.g., New York Heart Association Functional Class&#xD;
             III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias&#xD;
             requiring ongoing treatment, unstable angina or other significant cardiovascular&#xD;
             diseases);&#xD;
&#xD;
         13. History of thyroid disease poorly controlled on prescribed medications;&#xD;
&#xD;
         14. Evidence of severe retinopathy or clinically relevant ophthalmologic disorder;&#xD;
&#xD;
         15. History of other severe disease or evidence of other severe disease or any other&#xD;
             illness or conditions that the investigator believe that patients are not suitable to&#xD;
             join in the study;&#xD;
&#xD;
         16. Evidence of postoperative complications: infectious、bleeding, etc,. at baseline; or&#xD;
             evidence of recurrence or metastasis at baseline;&#xD;
&#xD;
         17. Child-Pugh scores :B、C&#xD;
&#xD;
         18. Patients included in another trial or having been given investigational drugs within&#xD;
             12 weeks prior to screening;&#xD;
&#xD;
         19. Other disease should exclusive considered by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lunxiu Qin</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jimimg Zhang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lunxiu Qin</last_name>
    <phone>52887172</phone>
    <email>qinlx@fudan.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Huliang Jia</last_name>
    <email>jbl-1@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Huashan Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lunxiu Qin</last_name>
      <phone>52887172</phone>
      <email>qinlx@fudan.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Huliang Jia</last_name>
      <email>jbl-1@163.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <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>Sohn W, Paik YH, Kim JM, Kwon CH, Joh JW, Cho JY, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. HBV DNA and HBsAg levels as risk predictors of early and late recurrence after curative resection of HBV-related hepatocellular carcinoma. Ann Surg Oncol. 2014 Jul;21(7):2429-35. doi: 10.1245/s10434-014-3621-x. Epub 2014 Mar 12.</citation>
    <PMID>24619495</PMID>
  </reference>
  <reference>
    <citation>Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, Panno AM, Bernardi M, Brander C, Bihl F, Andreone P, Maini MK. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013 Feb;58(2):225-33. doi: 10.1016/j.jhep.2012.09.029. Epub 2012 Oct 6.</citation>
    <PMID>23046671</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>September 6, 2017</last_update_submitted>
  <last_update_submitted_qc>September 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Huashan Hospital</investigator_affiliation>
    <investigator_full_name>Jiming Zhang</investigator_full_name>
    <investigator_title>Deputy director of department</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <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>Tenofovir</mesh_term>
    <mesh_term>Peginterferon alfa-2a</mesh_term>
    <mesh_term>Entecavir</mesh_term>
    <mesh_term>Adefovir</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/NCT03253250
org study id: PEG-HCC
nct id: NCT03253250
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The current study is a prospective, randomized, open, multi-center investigation. The aim of
      current study is to investigate whether the Recurrence-free Survival Rate (RFS）of the
      hepatitis B related -hepatocellular carcinoma subjects who have been treated by resection can
      be improved by peginterferon alfa-2a
The subjects who have been treated by resection due to hepatocellular carcinoma (HCC) will be
      randomized into 2 groups: the subjects in group A will be treated by Nucleotide analogues
      (NAs)( ETV, 0.5mg，qd；tenofovir disoproxil fumarate(TDF)，300mg，qd；ADV，10mg，qd）for 96 weeks;
      the subjects in group B will be treated by peginterferon alfa-2a （135μg/week）combination with
      NAs (ETV\TDF\ADV)for 96 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recurrence-free Survival Rate (RFS）
time frame: 2 years
description: Number of subjects without Recurrence in the total subjects
measure: Recurrence-free Survival Rate (RFS）
time frame: 1 year
description: Number of subjects without Recurrence in the total subjects
measure: Overall Survival Rate (OS）
time frame: 2 years
description: Number of subjects with survival in the total subjects
measure: Overall Survival Rate (OS）
time frame: 1 year
description: Number of subjects with survival in the total subjects
arm group label: Group A
arm group type: Active Comparator
description: The subjects will be treated by NAs (ETV, 0.5mg，qd；TDF，300mg，qd；ADV，10mg，qd）for 96 weeks
arm group label: Group B
arm group type: Experimental
description: The subjects will be treated by peginterferon alfa-2a （135μg/week）combination with NAs(ETV\TDF\ADV) for 96 weeks.
intervention type: Drug
intervention name: ETV；TDF；ADV
description: NAs
arm group label: Group A
arm group label: Group B
other name: entecavir;tenofovir disoproxil fumarate;adefovir
intervention type: Drug
intervention name: Peginterferon Alfa-2a
description: peginterferon
arm group label: Group B
other name: pegasys
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Lunxiu Qin
role: Principal Investigator
affiliation: Huashan Hospital
last name: Jimimg Zhang
role: Principal Investigator
affiliation: Huashan Hospital
last name: Lunxiu Qin
phone: 52887172
email: qinlx@fudan.edu.cn
last name: Huliang Jia
email: jbl-1@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
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: Sohn W, Paik YH, Kim JM, Kwon CH, Joh JW, Cho JY, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. HBV DNA and HBsAg levels as risk predictors of early and late recurrence after curative resection of HBV-related hepatocellular carcinoma. Ann Surg Oncol. 2014 Jul;21(7):2429-35. doi: 10.1245/s10434-014-3621-x. Epub 2014 Mar 12.
PMID: 24619495
citation: Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, Panno AM, Bernardi M, Brander C, Bihl F, Andreone P, Maini MK. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013 Feb;58(2):225-33. doi: 10.1016/j.jhep.2012.09.029. Epub 2012 Oct 6.
PMID: 23046671
responsible party type: Principal Investigator
investigator affiliation: Huashan Hospital
investigator full name: Jiming Zhang
investigator title: Deputy director of department
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Tenofovir
mesh term: Peginterferon alfa-2a
mesh term: Entecavir
mesh term: Adefovir