<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/NCT03782831</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-S066</org_study_id>
    <nct_id>NCT03782831</nct_id>
  </id_info>
  <brief_title>TACE Plus PD-1 Antibody vs TACE Alone for Unresectable HCC</brief_title>
  <official_title>Transarterial Chemoembolization Plus Programmed Cell Death Protein-1 Antibody Versus Transarterial Chemoembolization Alone for Unresectable Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kaiping Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangzhou No.12 People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to evaluate the efficacy and safety of transarterial&#xD;
      chemoembolization (TACE) combined with programmed cell death protein-1 (PD-1) antibody&#xD;
      compared with TACE Alone in patients with unresectable hepatocellular carcinoma (HCC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transarterial chemoembolization (TACE) is the first-line treatment for patients with&#xD;
      unrestable hepatocellular carcinoma (HCC) at intermediate-stage. Programmed cell death&#xD;
      protein-1 (PD-1) antibody is effective and safe for advanced HCC. No study has compared the&#xD;
      efficacy and safety of TACE plus PD-1 antibody and TACE alone. Thus, the investigators&#xD;
      carried out this prospective randomized control study to find out it.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No participants enrolled&#xD;
  </why_stopped>
  <start_date type="Actual">December 11, 2018</start_date>
  <completion_date type="Anticipated">June 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>12 months</time_frame>
    <description>PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>12 months</time_frame>
    <description>OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>12 months</time_frame>
    <description>ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>12 months</time_frame>
    <description>Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>TACE plus PD-1 antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients received hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA) on demand. In addition, patients received 3mg/kg PD-1 antibody intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TACE alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients received hepatic intra-arterial infusion with lipiodol mixed with hemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA) on demand. In addition, patients received placebos intravenously every 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>TACE</intervention_name>
    <description>Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA).</description>
    <arm_group_label>TACE alone</arm_group_label>
    <arm_group_label>TACE plus PD-1 antibody</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 antibody</intervention_name>
    <description>3mg/kg intravenously every 2 weeks</description>
    <arm_group_label>TACE plus PD-1 antibody</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>intravenous injection every 2 weeks</description>
    <arm_group_label>TACE alone</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  KPS≥70;&#xD;
&#xD;
          -  The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European&#xD;
             Association for the Study of the Liver (EASL), simultaneously staged as BCLC A or BCLC&#xD;
             B based on Barcelona Clinic Liver Cancer staging system.&#xD;
&#xD;
          -  Patients must have at least one tumor lesion that can be accurately measured;&#xD;
&#xD;
          -  Diagnosed as unresectable with consensus by the panel of liver surgery experts;&#xD;
&#xD;
          -  Re commanded treated by TACE with consensus by the panel of liver MDT;&#xD;
&#xD;
          -  No past history of TACE, chemotherapy or molecule-targeted treatment;&#xD;
&#xD;
          -  No Cirrhosis or cirrhotic status of Child-Pugh class A only&#xD;
&#xD;
          -  Meet the following laboratory parameters:(a) Platelet count ≥ 75,000/μL; (b)Hemoglobin&#xD;
             ≥ 8.5 g/dL;(c) Total bilirubin ≤ 30mmol/L;(d) Serum albumin&#xD;
&#xD;
             ≥ 32 g/L;(e) ASL and AST ≤ 6 x upper limit of normal;(f) Serum creatinine&#xD;
&#xD;
             ≤ 1.5 x upper limit of normal;(g) INR &gt; 2.3 or PT/APTT within normal limits; (h)&#xD;
             Absolute neutrophil count (ANC) &gt;1,500/mm3;&#xD;
&#xD;
          -  Ability to understand the protocol and to agree to and sign a written informed consent&#xD;
             document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with clinically significant gastrointestinal bleeding within 30 days prior to&#xD;
             study entry.&#xD;
&#xD;
          -  Known of serious heart disease which can nor endure the treatment such as cardiac&#xD;
             ventricular arrhythmias requiring anti-arrhythmic therapy&#xD;
&#xD;
          -  Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or&#xD;
             hepatic encephalopathy&#xD;
&#xD;
          -  Known history of HIV&#xD;
&#xD;
          -  History of organ allograft&#xD;
&#xD;
          -  Known or suspected allergy to the investigational agents or any agent given in&#xD;
             association with this trial.&#xD;
&#xD;
          -  Evidence of bleeding diathesis.&#xD;
&#xD;
          -  Any other hemorrhage/bleeding event &gt; CTCAE Grade 3 within 4 weeks of first dose of&#xD;
             study drug&#xD;
&#xD;
          -  Serious non-healing wound, ulcer, or bone fracture&#xD;
&#xD;
          -  Known central nervous system tumors including metastatic brain disease&#xD;
&#xD;
          -  Poor compliance that can not comply with the course of treatment and follow up.&#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>Ming Shi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Center Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guangzhou Twelfth People's Hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510620</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiping Central Hospital</name>
      <address>
        <city>Kaiping</city>
        <state>Guangdong</state>
        <zip>529300</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>April 30, 2019</last_update_submitted>
  <last_update_submitted_qc>April 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Shi Ming</investigator_full_name>
    <investigator_title>Proffessor</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Programmed cell death protein-1 antibody</keyword>
  <keyword>Transarterial chemoembolization</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>Antibodies</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/NCT03782831
org study id: HCC-S066
nct id: NCT03782831
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of transarterial
      chemoembolization (TACE) combined with programmed cell death protein-1 (PD-1) antibody
      compared with TACE Alone in patients with unresectable hepatocellular carcinoma (HCC)
Transarterial chemoembolization (TACE) is the first-line treatment for patients with
      unrestable hepatocellular carcinoma (HCC) at intermediate-stage. Programmed cell death
      protein-1 (PD-1) antibody is effective and safe for advanced HCC. No study has compared the
      efficacy and safety of TACE plus PD-1 antibody and TACE alone. Thus, the investigators
      carried out this prospective randomized control study to find out it.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Progression Free Survival (PFS)
time frame: 12 months
description: PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.
measure: Overall Survival (OS)
time frame: 12 months
description: OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.
measure: Objective Response Rate (ORR)
time frame: 12 months
description: ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.
measure: Adverse Events
time frame: 12 months
description: Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03
arm group label: TACE plus PD-1 antibody
arm group type: Experimental
description: Patients received hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA) on demand. In addition, patients received 3mg/kg PD-1 antibody intravenously every 2 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
arm group label: TACE alone
arm group type: Active Comparator
description: Patients received hepatic intra-arterial infusion with lipiodol mixed with hemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA) on demand. In addition, patients received placebos intravenously every 2 weeks
intervention type: Procedure
intervention name: TACE
description: Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA).
arm group label: TACE alone
arm group label: TACE plus PD-1 antibody
intervention type: Drug
intervention name: PD-1 antibody
description: 3mg/kg intravenously every 2 weeks
arm group label: TACE plus PD-1 antibody
intervention type: Drug
intervention name: Placebos
description: intravenous injection every 2 weeks
arm group label: TACE alone
other name: normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ming Shi, MD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
facility: 
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Shi Ming
investigator title: Proffessor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Antibodies