<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/NCT04414956</url>
  </required_header>
  <id_info>
    <org_study_id>HCCAFPL3</org_study_id>
    <nct_id>NCT04414956</nct_id>
  </id_info>
  <brief_title>Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) and Image Tools for Early Detection of Hepatocellular Carcinoma</brief_title>
  <official_title>Clinical Usefulness of Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) With Abdominal Sonography or Computed Tomography for Early Detection of Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korea University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Korea University Ansan Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Soonchunhyang University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korea University Guro Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Catholic University of Korea</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korea University Anam Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Keimyung University Dongsan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hanyang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Konkuk University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Inje University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chung-Ang University Hosptial, Chung-Ang University College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Korea University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, three biomarkers tests (AFP, AFP-L3 and PIVKA-II) and abdominal sonography or&#xD;
      CT scans are performed every 6 months to detect hepatocellular carcinoma (HCC) early in&#xD;
      patients with cirrhosis, a high-risk group of HCC. The aim of this study is to confirm the&#xD;
      early HCC diagnosis rate in patients with cirrhosis and compare the detection efficacy&#xD;
      between tests.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Early diagnosis of HCC is the most important factor in improving the prognosis of the&#xD;
      disease. A surveillance test for early diagnosis of HCC in Korea is to perform alfa&#xD;
      fetoprotein (AFP) and abdominal sonography every 6-months in high-risk groups. However, the&#xD;
      detection rate of HCC using AFP and abdominal sonography is very low. There are several&#xD;
      reports that the combination of the multiple biomarker tests including AFP, AFP L3, and&#xD;
      PIVKA-II increased the early HCC detection only one test. Therefore, in the surveillance test&#xD;
      for HCC, the combination of three tests with sonography would be helpful in the early&#xD;
      diagnosis of HCC. However, there was few prospective large-scale studies about this issue.&#xD;
&#xD;
      Compared with abdominal sonography, contrast-enhanced CT or MRI is more useful in finding&#xD;
      intrahepatic lesions of liver cirrhosis. However, there is no evidence data on combining&#xD;
      sono/CT and biomarkers could improve the diagnosis for early HCC. Thus, it is essential to&#xD;
      verify this prospectively in the real clinical practices to make recommendations based on a&#xD;
      high level of evidence in the future. The investigators are conducting a prospective study&#xD;
      which examines three biomarker tests and sonography every six months and contrast-enhanced CT&#xD;
      annually for HCC surveillance in patients with cirrhosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2016</start_date>
  <completion_date type="Anticipated">February 28, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Patients with cirrhosis will receive the surveillance test using three biomarker tests and sonography every six months and contrast-enhanced CT annually</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HCC occurrence</measure>
    <time_frame>3 years after enrollment</time_frame>
    <description>Detection of HCC occurrence by three biomarkers and two image modalities</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Early HCC occurrence</measure>
    <time_frame>3 years after enrollment</time_frame>
    <description>Detection of HCC less than 2cm</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1418</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Surveillance</condition>
  <arm_group>
    <arm_group_label>Surveillance</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>AFP-L3</intervention_name>
    <description>AFP-L3 will be tested using serum sample every 6 months.</description>
    <arm_group_label>Surveillance</arm_group_label>
    <other_name>Lens culinaris agglutinin-reactive fraction of AFP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>AFP</intervention_name>
    <description>AFP will be tested using serum sample every 6 months.</description>
    <arm_group_label>Surveillance</arm_group_label>
    <other_name>Alpha fetoprotein</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>PIVKA-II</intervention_name>
    <description>PIVKA-II will be tested using serum sample every 6 months.</description>
    <arm_group_label>Surveillance</arm_group_label>
    <other_name>Protein induced by vitamin K absence or antagonist-II</other_name>
    <other_name>des-gamma-carboxy prothrombin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Sonography</intervention_name>
    <description>Sonography will be tested by experts every 6 months.</description>
    <arm_group_label>Surveillance</arm_group_label>
    <other_name>Ultrasound</other_name>
    <other_name>US</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CT</intervention_name>
    <description>Contrast-enhanced CT will be tested annually.</description>
    <arm_group_label>Surveillance</arm_group_label>
    <other_name>Computed tomography</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with liver cirrhosis meeting one of the followings:&#xD;
&#xD;
             i. Histologically confirmed liver cirrhosis ii. Imaging findings with liver cirrhosis&#xD;
             (liver surface undulation, irregularity, or nodularity by US, CT, or MRI) plus one of&#xD;
             followings: liver stiffness measurement ≥ 12.5 kilopascal, esophago-gastric varices,&#xD;
             thrombocytopenia (&lt;120,000/mm3), hypoalbuminemia (&lt;3.5 g/dL), splenomegaly ≥12 cm)&#xD;
             iii. Imaging findings with liver cirrhosis together with biomarkers suggesting liver&#xD;
             cirrhosis (APRI ≥2.0 or fibrosis-4 ≥3.6) iv. Imaging findings with liver cirrhosis&#xD;
             with history of hepatic decompensation (ascites, esophago-gastric variceal bleeding,&#xD;
             jaundice, hepatic encephalopathy))&#xD;
&#xD;
          -  Expected survival more than 1 year&#xD;
&#xD;
          -  Child Pugh score 5-10 at the time of enrollment&#xD;
&#xD;
          -  Serum creatinine ≤1.5mg/dL&#xD;
&#xD;
          -  Age between 19 and 75 years old&#xD;
&#xD;
          -  No significant underlying medical illness affecting patient's survival&#xD;
&#xD;
          -  Patients available for regular follow-up according to the study protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of HCC&#xD;
&#xD;
          -  AFP &gt;20 ng/mL&#xD;
&#xD;
          -  Hepatic nodule ≥ 1 cm by US or CT Exceptionally, nodules showing characteristic&#xD;
             features of benign lesion such as hemangioma or pathologically conformed benign lesion&#xD;
             are permitted for study inclusion.&#xD;
&#xD;
          -  Hepatic nodule less than 1 cm on US but imaging findings suggesting HCC by contrast&#xD;
             enhanced US, CT, or MRI&#xD;
&#xD;
          -  Child-Pugh score ≥ 11&#xD;
&#xD;
          -  History of liver transplantation&#xD;
&#xD;
          -  Expecting liver transplantation within 1 year&#xD;
&#xD;
          -  Hypersensitivity on CT contrast dye&#xD;
&#xD;
          -  Any contraindication for CT&#xD;
&#xD;
          -  Not able to perform abdominal US&#xD;
&#xD;
          -  Other uncontrolled malignancy&#xD;
&#xD;
          -  Patients taking warfarin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hyung Joon Yim, MD,PhD</last_name>
    <phone>+82-31-412-6565</phone>
    <email>gudwns21@korea.ac.kr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Soon Ho Um, MD,PhD</last_name>
    <phone>+82-2-920-5019</phone>
    <email>umsh@korea.ac.kr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Korea University Ansan Hospital</name>
      <address>
        <city>Ansan</city>
        <state>Gyeonggi-do</state>
        <zip>15355</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hyung Joon Yim</last_name>
      <phone>+82-31-412-6565</phone>
      <email>gudwns21@korea.ac.kr</email>
    </contact>
    <contact_backup>
      <last_name>Tae Hyung Kim</last_name>
      <phone>+82-31-412-4832</phone>
      <email>lacid@korea.ac.kr</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Uijeongbu St.Mary's Hospital</name>
      <address>
        <city>Uijeongbu</city>
        <state>Gyeonggi-do</state>
        <zip>11765</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Changwook Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Keimyung University Dongsan Medical Center</name>
      <address>
        <city>Daegu</city>
        <zip>42601</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Byoungkuk Jang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inje University SangGye Paik Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>01757</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eileen L. Yoon</last_name>
      <email>mseileen80@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Soon Ho Um</last_name>
      <phone>+82-2-920-6555</phone>
      <email>umsh@korea.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yunjoon Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Doyoung Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Soonchunhyang University Seoul Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>04401</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jae Young Jang</last_name>
      <email>jyjang@schmc.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hanyang University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>04763</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>DaeWon Jun</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Konkuk University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>05030</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wonhyeok Choe</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Youngseok Yim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yonghan Paik</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Seoul St.Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeong Won Jang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chung-Ang University Hosptial</name>
      <address>
        <city>Seoul</city>
        <zip>06973</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hyungjoon Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Guro Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>08308</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ji Hoon Kim</last_name>
      <email>kjhhepar@naver.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.</citation>
    <PMID>21992124</PMID>
  </reference>
  <reference>
    <citation>Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015 May 23;9(3):267-317. doi: 10.5009/gnl14460.</citation>
    <PMID>25918260</PMID>
  </reference>
  <reference>
    <citation>Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015 Apr 7;21(13):3826-42. doi: 10.3748/wjg.v21.i13.3826.</citation>
    <PMID>25852267</PMID>
  </reference>
  <reference>
    <citation>European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available. Erratum In: J Hepatol. 2012 Jun;56(6):1430.</citation>
    <PMID>22424438</PMID>
  </reference>
  <results_reference>
    <citation>Yim SY, Seo YS, Jung CH, Kim TH, Lee JM, Kim ES, Keum B, Jong YK, An H, Kim JH, Yim HJ, Kim DS, Jeen YT, Yeon JE, Lee HS, Chun HJ, Byun KS, Um SH, Kim CD, Ryu HS. The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years? Liver Int. 2016 Mar;36(3):445-53. doi: 10.1111/liv.12960. Epub 2015 Oct 12.</citation>
    <PMID>26352789</PMID>
  </results_reference>
  <results_reference>
    <citation>Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, Schwartz ME, Sherman M. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009 Jan;7(1):104-13. doi: 10.1016/j.cgh.2008.08.041. Epub 2008 Sep 17.</citation>
    <PMID>18849011</PMID>
  </results_reference>
  <results_reference>
    <citation>Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo Y, Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology. 1990 Aug;99(2):508-18. doi: 10.1016/0016-5085(90)91034-4.</citation>
    <PMID>1694805</PMID>
  </results_reference>
  <results_reference>
    <citation>Taketa K, Endo Y, Sekiya C, Tanikawa K, Koji T, Taga H, Satomura S, Matsuura S, Kawai T, Hirai H. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res. 1993 Nov 15;53(22):5419-23.</citation>
    <PMID>7693340</PMID>
  </results_reference>
  <results_reference>
    <citation>Oka H, Saito A, Ito K, Kumada T, Satomura S, Kasugai H, Osaki Y, Seki T, Kudo M, Tanaka M; Collaborative Hepato-Oncology Study Group of Japan. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol. 2001 Dec;16(12):1378-83. doi: 10.1046/j.1440-1746.2001.02643.x.</citation>
    <PMID>11851836</PMID>
  </results_reference>
  <results_reference>
    <citation>Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E, Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006 Sep;101(9):2038-43. doi: 10.1111/j.1572-0241.2006.00681.x. Epub 2006 Jul 18.</citation>
    <PMID>16848811</PMID>
  </results_reference>
  <results_reference>
    <citation>Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG, Oh EJ. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21;19(3):339-46. doi: 10.3748/wjg.v19.i3.339.</citation>
    <PMID>23372355</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol. 2009;44(7):861-6. doi: 10.1080/00365520902903034.</citation>
    <PMID>19391065</PMID>
  </results_reference>
  <results_reference>
    <citation>Seo SI, Kim HS, Kim WJ, Shin WG, Kim DJ, Kim KH, Jang MK, Lee JH, Kim JS, Kim HY, Kim DJ, Lee MS, Park CK. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2015 Apr 7;21(13):3928-35. doi: 10.3748/wjg.v21.i13.3928.</citation>
    <PMID>25852278</PMID>
  </results_reference>
  <results_reference>
    <citation>Lim TS, Kim DY, Han KH, Kim HS, Shin SH, Jung KS, Kim BK, Kim SU, Park JY, Ahn SH. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients. Scand J Gastroenterol. 2016 Mar;51(3):344-53. doi: 10.3109/00365521.2015.1082190. Epub 2015 Sep 4.</citation>
    <PMID>26340708</PMID>
  </results_reference>
  <results_reference>
    <citation>Di Martino M, De Filippis G, De Santis A, Geiger D, Del Monte M, Lombardo CV, Rossi M, Corradini SG, Mennini G, Catalano C. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging. Eur Radiol. 2013 Apr;23(4):887-96. doi: 10.1007/s00330-012-2691-z. Epub 2012 Nov 18.</citation>
    <PMID>23179521</PMID>
  </results_reference>
  <results_reference>
    <citation>Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, Okusaka T, Miyayama S, Tsuchiya K, Ueshima K, Hiraoka A, Ikeda M, Ogasawara S, Yamashita T, Minami T, Yamakado K; Liver Cancer Study Group of Japan. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014 Oct;3(3-4):458-68. doi: 10.1159/000343875.</citation>
    <PMID>26280007</PMID>
  </results_reference>
  <results_reference>
    <citation>Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, Zakher B, Pappas M, Graham E, Sullivan SD. Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 May 19;162(10):697-711. doi: 10.7326/M14-2509. Erratum In: Ann Intern Med. 2015 Jun 16;162(12):880.</citation>
    <PMID>25984845</PMID>
  </results_reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>May 30, 2020</last_update_submitted>
  <last_update_submitted_qc>May 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Korea University</investigator_affiliation>
    <investigator_full_name>Soon Ho Um</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Liver Cirrhosis</keyword>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>Surveillance</keyword>
  <keyword>AFP-L3</keyword>
  <keyword>AFP</keyword>
  <keyword>PIVKA-II</keyword>
  <keyword>Sonography</keyword>
  <keyword>CT</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>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin K</mesh_term>
    <mesh_term>Agglutinins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04414956
org study id: HCCAFPL3
nct id: NCT04414956
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this study, three biomarkers tests (AFP, AFP-L3 and PIVKA-II) and abdominal sonography or
      CT scans are performed every 6 months to detect hepatocellular carcinoma (HCC) early in
      patients with cirrhosis, a high-risk group of HCC. The aim of this study is to confirm the
      early HCC diagnosis rate in patients with cirrhosis and compare the detection efficacy
      between tests.
Early diagnosis of HCC is the most important factor in improving the prognosis of the
      disease. A surveillance test for early diagnosis of HCC in Korea is to perform alfa
      fetoprotein (AFP) and abdominal sonography every 6-months in high-risk groups. However, the
      detection rate of HCC using AFP and abdominal sonography is very low. There are several
      reports that the combination of the multiple biomarker tests including AFP, AFP L3, and
      PIVKA-II increased the early HCC detection only one test. Therefore, in the surveillance test
      for HCC, the combination of three tests with sonography would be helpful in the early
      diagnosis of HCC. However, there was few prospective large-scale studies about this issue.

      Compared with abdominal sonography, contrast-enhanced CT or MRI is more useful in finding
      intrahepatic lesions of liver cirrhosis. However, there is no evidence data on combining
      sono/CT and biomarkers could improve the diagnosis for early HCC. Thus, it is essential to
      verify this prospectively in the real clinical practices to make recommendations based on a
      high level of evidence in the future. The investigators are conducting a prospective study
      which examines three biomarker tests and sonography every six months and contrast-enhanced CT
      annually for HCC surveillance in patients with cirrhosis.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Patients with cirrhosis will receive the surveillance test using three biomarker tests and sonography every six months and contrast-enhanced CT annually
primary purpose: Screening
masking: None (Open Label)
measure: HCC occurrence
time frame: 3 years after enrollment
description: Detection of HCC occurrence by three biomarkers and two image modalities
measure: Early HCC occurrence
time frame: 3 years after enrollment
description: Detection of HCC less than 2cm
arm group label: Surveillance
arm group type: Other
description: All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.
intervention type: Diagnostic Test
intervention name: AFP-L3
description: AFP-L3 will be tested using serum sample every 6 months.
arm group label: Surveillance
other name: Lens culinaris agglutinin-reactive fraction of AFP
intervention type: Diagnostic Test
intervention name: AFP
description: AFP will be tested using serum sample every 6 months.
arm group label: Surveillance
other name: Alpha fetoprotein
intervention type: Diagnostic Test
intervention name: PIVKA-II
description: PIVKA-II will be tested using serum sample every 6 months.
arm group label: Surveillance
other name: Protein induced by vitamin K absence or antagonist-II
other name: des-gamma-carboxy prothrombin
intervention type: Diagnostic Test
intervention name: Sonography
description: Sonography will be tested by experts every 6 months.
arm group label: Surveillance
other name: Ultrasound
other name: US
intervention type: Diagnostic Test
intervention name: CT
description: Contrast-enhanced CT will be tested annually.
arm group label: Surveillance
other name: Computed tomography
criteria: 
gender: All
minimum age: 19 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hyung Joon Yim, MD,PhD
phone: +82-31-412-6565
email: gudwns21@korea.ac.kr
last name: Soon Ho Um, MD,PhD
phone: +82-2-920-5019
email: umsh@korea.ac.kr
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
citation: El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.
PMID: 21992124
citation: Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015 May 23;9(3):267-317. doi: 10.5009/gnl14460.
PMID: 25918260
citation: Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015 Apr 7;21(13):3826-42. doi: 10.3748/wjg.v21.i13.3826.
PMID: 25852267
citation: European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available. Erratum In: J Hepatol. 2012 Jun;56(6):1430.
PMID: 22424438
citation: Yim SY, Seo YS, Jung CH, Kim TH, Lee JM, Kim ES, Keum B, Jong YK, An H, Kim JH, Yim HJ, Kim DS, Jeen YT, Yeon JE, Lee HS, Chun HJ, Byun KS, Um SH, Kim CD, Ryu HS. The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years? Liver Int. 2016 Mar;36(3):445-53. doi: 10.1111/liv.12960. Epub 2015 Oct 12.
PMID: 26352789
citation: Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, Schwartz ME, Sherman M. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009 Jan;7(1):104-13. doi: 10.1016/j.cgh.2008.08.041. Epub 2008 Sep 17.
PMID: 18849011
citation: Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo Y, Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology. 1990 Aug;99(2):508-18. doi: 10.1016/0016-5085(90)91034-4.
PMID: 1694805
citation: Taketa K, Endo Y, Sekiya C, Tanikawa K, Koji T, Taga H, Satomura S, Matsuura S, Kawai T, Hirai H. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res. 1993 Nov 15;53(22):5419-23.
PMID: 7693340
citation: Oka H, Saito A, Ito K, Kumada T, Satomura S, Kasugai H, Osaki Y, Seki T, Kudo M, Tanaka M; Collaborative Hepato-Oncology Study Group of Japan. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol. 2001 Dec;16(12):1378-83. doi: 10.1046/j.1440-1746.2001.02643.x.
PMID: 11851836
citation: Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E, Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006 Sep;101(9):2038-43. doi: 10.1111/j.1572-0241.2006.00681.x. Epub 2006 Jul 18.
PMID: 16848811
citation: Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG, Oh EJ. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21;19(3):339-46. doi: 10.3748/wjg.v19.i3.339.
PMID: 23372355
citation: Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol. 2009;44(7):861-6. doi: 10.1080/00365520902903034.
PMID: 19391065
citation: Seo SI, Kim HS, Kim WJ, Shin WG, Kim DJ, Kim KH, Jang MK, Lee JH, Kim JS, Kim HY, Kim DJ, Lee MS, Park CK. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2015 Apr 7;21(13):3928-35. doi: 10.3748/wjg.v21.i13.3928.
PMID: 25852278
citation: Lim TS, Kim DY, Han KH, Kim HS, Shin SH, Jung KS, Kim BK, Kim SU, Park JY, Ahn SH. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients. Scand J Gastroenterol. 2016 Mar;51(3):344-53. doi: 10.3109/00365521.2015.1082190. Epub 2015 Sep 4.
PMID: 26340708
citation: Di Martino M, De Filippis G, De Santis A, Geiger D, Del Monte M, Lombardo CV, Rossi M, Corradini SG, Mennini G, Catalano C. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging. Eur Radiol. 2013 Apr;23(4):887-96. doi: 10.1007/s00330-012-2691-z. Epub 2012 Nov 18.
PMID: 23179521
citation: Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, Okusaka T, Miyayama S, Tsuchiya K, Ueshima K, Hiraoka A, Ikeda M, Ogasawara S, Yamashita T, Minami T, Yamakado K; Liver Cancer Study Group of Japan. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014 Oct;3(3-4):458-68. doi: 10.1159/000343875.
PMID: 26280007
citation: Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, Zakher B, Pappas M, Graham E, Sullivan SD. Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 May 19;162(10):697-711. doi: 10.7326/M14-2509. Erratum In: Ann Intern Med. 2015 Jun 16;162(12):880.
PMID: 25984845
responsible party type: Principal Investigator
investigator affiliation: Korea University
investigator full name: Soon Ho Um
investigator title: Professor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Cirrhosis
mesh term: Fibrosis
mesh term: Vitamin K
mesh term: Agglutinins
sharing ipd: No