<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/NCT03780634</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-S059</org_study_id>
    <nct_id>NCT03780634</nct_id>
  </id_info>
  <brief_title>HAIC Plus PD-1 Antibody vs HAIC Plus Sorafenib for Advanced HCC</brief_title>
  <official_title>Hepatic Artery Infusion Chemotherapy Plus Programmed Cell Death Protein-1 (PD-1) Antibody vs Hepatic Artery Infusion Chemotherapy Plus Sorafenib for Advanced 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 hepatic artery infusion&#xD;
      chemotherapy (HAIC) combined with Programmed Cell Death Protein-1 (PD-1) antibody compared&#xD;
      with HAIC plus sorafenib in patients with advanced hepatocellular carcinoma (HCC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The results of our preliminary pilot study suggested that sorafenib combined with hepatic&#xD;
      arterial infusion chemotherapy (HAIC) may improve the survivals for advanced hepatocellular&#xD;
      (HCC). Programmed Cell Death Protein-1 (PD-1) antibody has been proved effective and safety&#xD;
      for advanced HCC. There is no study about HAIC plus PD-1 antibody. Thus, the investigators&#xD;
      carried out this prospective randomized control study to compare HAIC plus sorafenib and HAIC&#xD;
      plus PD-1 antibody.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No participants enrolled&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 1, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2020</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>None (Open Label)</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 Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 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 RECIST.</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>HAIC plus PD-1 antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received PD-1 antibody intravenously and hepatic artery infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HAIC plus sorafenib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants received sorafenib capsules 400mg bid in continuous 21-day treatment cycles, and received hepatic artery infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>HAIC</intervention_name>
    <description>administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks</description>
    <arm_group_label>HAIC plus PD-1 antibody</arm_group_label>
    <arm_group_label>HAIC plus sorafenib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 antibody</intervention_name>
    <description>200mg intravenously every 3 weeks</description>
    <arm_group_label>HAIC plus PD-1 antibody</arm_group_label>
    <other_name>Programmed cell death 1 antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>400 mg Bid Po</description>
    <arm_group_label>HAIC plus sorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#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)&#xD;
&#xD;
          -  Patients must have at least one tumor lesion that can be accurately measured according&#xD;
             to EASL criteria.&#xD;
&#xD;
          -  Barcelona clinic liver cancer-stage C&#xD;
&#xD;
          -  Major portal vein tumor thrombus (Vp3,Vp4)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0 to 1&#xD;
&#xD;
          -  with no previous treatment&#xD;
&#xD;
          -  No Cirrhosis or cirrhotic status of Child-Pugh class A only&#xD;
&#xD;
          -  Not amendable to surgical resection, local ablative therapy and any other cured&#xD;
             treatment.&#xD;
&#xD;
          -  The following laboratory parameters:&#xD;
&#xD;
               -  Platelet count ≥ 75,000/μL&#xD;
&#xD;
               -  Hemoglobin ≥ 8.5 g/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 30mmol/L&#xD;
&#xD;
               -  Serum albumin ≥ 30 g/L&#xD;
&#xD;
               -  ASL and AST ≤ 5 x upper limit of normal&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x upper limit of normal&#xD;
&#xD;
               -  INR ≤ 1.5 or PT/APTT within normal limits&#xD;
&#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;
          -  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;
          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy&#xD;
&#xD;
          -  Evidence of bleeding diathesis.&#xD;
&#xD;
          -  Patients with clinically significant gastrointestinal bleeding within 30 days prior to&#xD;
             study entry.&#xD;
&#xD;
          -  Known central nervous system tumors including metastatic brain disease&#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>March 2019</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>May 2, 2019</last_update_submitted>
  <last_update_submitted_qc>May 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 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>Hepatic arterial infusion chemotherapy</keyword>
  <keyword>Programmed cell death protein-1 antibody</keyword>
  <keyword>Oxaliplatin, 5-Fluorouracil and Leucovorin</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>Sorafenib</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</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/NCT03780634
org study id: HCC-S059
nct id: NCT03780634
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 hepatic artery infusion
      chemotherapy (HAIC) combined with Programmed Cell Death Protein-1 (PD-1) antibody compared
      with HAIC plus sorafenib in patients with advanced hepatocellular carcinoma (HCC)
The results of our preliminary pilot study suggested that sorafenib combined with hepatic
      arterial infusion chemotherapy (HAIC) may improve the survivals for advanced hepatocellular
      (HCC). Programmed Cell Death Protein-1 (PD-1) antibody has been proved effective and safety
      for advanced HCC. There is no study about HAIC plus PD-1 antibody. Thus, the investigators
      carried out this prospective randomized control study to compare HAIC plus sorafenib and HAIC
      plus PD-1 antibody.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
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 Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 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 RECIST.
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: HAIC plus PD-1 antibody
arm group type: Experimental
description: Participants received PD-1 antibody intravenously and hepatic artery infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
arm group label: HAIC plus sorafenib
arm group type: Active Comparator
description: Participants received sorafenib capsules 400mg bid in continuous 21-day treatment cycles, and received hepatic artery infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
intervention type: Procedure
intervention name: HAIC
description: administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks
arm group label: HAIC plus PD-1 antibody
arm group label: HAIC plus sorafenib
intervention type: Drug
intervention name: PD-1 antibody
description: 200mg intravenously every 3 weeks
arm group label: HAIC plus PD-1 antibody
other name: Programmed cell death 1 antibody
intervention type: Drug
intervention name: Sorafenib
description: 400 mg Bid Po
arm group label: HAIC plus sorafenib
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: Sorafenib
mesh term: Antibodies
mesh term: Immunoglobulins