<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/NCT02967887</url>
  </required_header>
  <id_info>
    <org_study_id>CBS-PCT-01</org_study_id>
    <nct_id>NCT02967887</nct_id>
  </id_info>
  <brief_title>Evaluation of Hepatic Arterial Infusion of Cisplatin and 5-FU in Biomarker Stratified HCC</brief_title>
  <acronym>SHINE</acronym>
  <official_title>Single-arm, Prospective, Multicenter Clinical Trial to Assess the Efficacy and the Safety of Combination Therapy of Hepatic Arterial Infusion of Cisplatin and 5-FU in Advanced Hepatocellular Carcinoma With Low Expression of HMGB2 Biomarker</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CbsBioscience</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CbsBioscience</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to assess the efficacy and the safety of hepatic arterial infusion of cisplatin&#xD;
      and 5-fluorouracil (HAIC) in advanced HCC patients stratified by biomarker expression&#xD;
      predicting therapeutic response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and 5-fluorouracil has been used&#xD;
      in advanced HCC. However, cisplatin or 5-fluorouracil acts on cells without tumor&#xD;
      selectivity. Therefore, to improve the tumor selectivity and effectiveness of HAIC, molecular&#xD;
      subtyping-based stratification strategies should be considered. In this study, patients who&#xD;
      have progressed or intolerance to sorafenib with non-metastatic HCC in TNM stage III-IVA and&#xD;
      ECOG PS 0 or 1, Child-Pugh class A will be enrolled. 96 patients with pre-treatment tumor&#xD;
      biopsy will receive Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h&#xD;
      on days 1-3) through implanted port system. This treatment will be repeated every 4 weeks, up&#xD;
      to 6 times. The primary objective is to determine overall response rate, where benefit is&#xD;
      defined as complete or partial response according to mRECIST V1.1. Secondary endpoints&#xD;
      include time to progression, progression free survival. The biopsy tissue will be subjected&#xD;
      to real time reverse transcriptase polymerase chain reaction for quantification of gene&#xD;
      expression levels. Patients will be categorized into two groups according to gene expression&#xD;
      results, and then AUC value of ROC curve analysis will be evaluated as an exploratory&#xD;
      endpoint to assess predictive performance of biomarker for therapeutic response of HAIC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">October 2018</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective tumor response</measure>
    <time_frame>Approximately 6 months</time_frame>
    <description>Objective tumor response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) assessed by radiological review</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time-to-Progression</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free-survival</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory endpoint: Diagnostic performance of biomarkers</measure>
    <time_frame>Through study completion, an average of 3 months</time_frame>
    <description>Patients will be categorized according to the result of biomarker expression and then AUC value of ROC curve analysis will be evaluated as an exploratory endpoint to assess predictive performance of biomarkers for therapeutic response of drugs.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Hepatocellular Carcinoma Non-Resectable</condition>
  <arm_group>
    <arm_group_label>cisplatin and 5-fluorouracil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enrolled patients with pre-treatment tumor biopsy will receive Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system. This treatment will be repeated every 4 weeks, up to 6 times.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin and 5-fluorouracil</intervention_name>
    <description>Hepatic arterial infusion of Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system (chemoport)</description>
    <arm_group_label>cisplatin and 5-fluorouracil</arm_group_label>
    <other_name>CBD-01 and CBD-02</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  over 20 years old&#xD;
&#xD;
          -  Patients with advanced hepatocellular carcinoma who have progressed or intolerance to&#xD;
             Sorafenib&#xD;
&#xD;
          -  Patients with advanced hepatocellular carcinoma who cannot be treated with surgery,&#xD;
             transplantation, RFA, or TACE.&#xD;
&#xD;
          -  TNM stage III/IV (including intrahepatic single or multiple tumors without&#xD;
             extrahepatic metastasis regardless of lymph node metastasis)&#xD;
&#xD;
          -  ECOG performance status of 0 or 1&#xD;
&#xD;
          -  Liver function status of Child-Pugh Class A or B&#xD;
&#xD;
          -  more than 3 months of life expectancy&#xD;
&#xD;
          -  serum creatinine &lt;1.5 mg/dL&#xD;
&#xD;
          -  aminotransferase &lt;5 times the upper limit of normal&#xD;
&#xD;
          -  absolute neutrophil count &gt;1,500 cells/lL&#xD;
&#xD;
          -  platelet count &gt;75,000/lL&#xD;
&#xD;
          -  hemoglobin &gt;10 g/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients with extrahepatic tumors&#xD;
&#xD;
          -  Patients requiring combined treatment with chemotherapy, radiotherapy, TACE, RFA, or&#xD;
             others&#xD;
&#xD;
          -  Patients in any severe and/or uncontrolled medical conditions&#xD;
&#xD;
          -  patients with history of allergic response to CT contrast media&#xD;
&#xD;
          -  patients who participated as subjects in other interventional clinical studies (as of&#xD;
             the date of visit) within 60 days before drug administration&#xD;
&#xD;
          -  Any person deemed inappropriate by reason of the investigator for other reasons&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Si Hyun Bae, MD., PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Catholic University of Korea</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Young Park</last_name>
    <phone>82-2-336-0855</phone>
    <email>jonnypark@cbsbio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Korea University Ansan Hospital</name>
      <address>
        <city>Ansan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yim, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sooncheonhyang University Hospital Bucheon</name>
      <address>
        <city>Bucheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kim, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Bucheon ST. Mary's Hospital</name>
      <address>
        <city>Bucheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lee, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Keimyung University Dongsan Medical Center</name>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Chung, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Daejeon ST. Mary's Hospital</name>
      <address>
        <city>Daejeon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Song, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chonnam National University Hwasun Hospital</name>
      <address>
        <city>Hwasun</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Cho, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Seo, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yoon, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sooncheonhyang University Hospital Seoul</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jang, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Catholic University of korea, Seoul ST. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Si Hyun Bae, MD., PhD.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wang, MD., PhD.</last_name>
    </contact>
    <contact_backup>
      <last_name>Cheong, MD., PhD.</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea ST. Vincent's Hospital</name>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Song, MD., PhD.</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>November 10, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>July 13, 2017</last_update_submitted>
  <last_update_submitted_qc>July 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Fluorouracil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02967887
org study id: CBS-PCT-01
nct id: NCT02967887
lead sponsor: 
has dmc: Yes
This study is to assess the efficacy and the safety of hepatic arterial infusion of cisplatin
      and 5-fluorouracil (HAIC) in advanced HCC patients stratified by biomarker expression
      predicting therapeutic response.
Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and 5-fluorouracil has been used
      in advanced HCC. However, cisplatin or 5-fluorouracil acts on cells without tumor
      selectivity. Therefore, to improve the tumor selectivity and effectiveness of HAIC, molecular
      subtyping-based stratification strategies should be considered. In this study, patients who
      have progressed or intolerance to sorafenib with non-metastatic HCC in TNM stage III-IVA and
      ECOG PS 0 or 1, Child-Pugh class A will be enrolled. 96 patients with pre-treatment tumor
      biopsy will receive Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h
      on days 1-3) through implanted port system. This treatment will be repeated every 4 weeks, up
      to 6 times. The primary objective is to determine overall response rate, where benefit is
      defined as complete or partial response according to mRECIST V1.1. Secondary endpoints
      include time to progression, progression free survival. The biopsy tissue will be subjected
      to real time reverse transcriptase polymerase chain reaction for quantification of gene
      expression levels. Patients will be categorized into two groups according to gene expression
      results, and then AUC value of ROC curve analysis will be evaluated as an exploratory
      endpoint to assess predictive performance of biomarker for therapeutic response of HAIC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective tumor response
time frame: Approximately 6 months
description: Objective tumor response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) assessed by radiological review
measure: Time-to-Progression
time frame: Approximately 24 months
measure: Progression-free-survival
time frame: Approximately 24 months
measure: Exploratory endpoint: Diagnostic performance of biomarkers
time frame: Through study completion, an average of 3 months
description: Patients will be categorized according to the result of biomarker expression and then AUC value of ROC curve analysis will be evaluated as an exploratory endpoint to assess predictive performance of biomarkers for therapeutic response of drugs.
arm group label: cisplatin and 5-fluorouracil
arm group type: Experimental
description: Enrolled patients with pre-treatment tumor biopsy will receive Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system. This treatment will be repeated every 4 weeks, up to 6 times.
intervention type: Drug
intervention name: cisplatin and 5-fluorouracil
description: Hepatic arterial infusion of Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system (chemoport)
arm group label: cisplatin and 5-fluorouracil
other name: CBD-01 and CBD-02
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Si Hyun Bae, MD., PhD.
role: Principal Investigator
affiliation: The Catholic University of Korea
last name: Jin Young Park
phone: 82-2-336-0855
email: jonnypark@cbsbio.com
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Fluorouracil
sharing ipd: Undecided