<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/NCT02973685</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-S023</org_study_id>
    <nct_id>NCT02973685</nct_id>
  </id_info>
  <brief_title>HAIC Versus TACE for Large Hepatocellular Carcinoma Staged BCLC A/B.</brief_title>
  <official_title>The Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Compared With Transarterial Chemoembolization as Initial Treatment in Patients With Large Hepatocellular Carcinoma Staged BCLC A/B.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guangzhou No.12 People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First People's Hospital of Foshan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion&#xD;
      chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) in patients with&#xD;
      large hepatocellular carcinoma staged BCLC A/B.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transarterial chemoembolization (TACE) is the most widely used palliative treatment for&#xD;
      hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect of&#xD;
      TACE for patients with large hepatocellular carcinoma staged BCLC A/B especially for those&#xD;
      with tumor larger than 10 cm. Our previous prospective study also revealed similar results of&#xD;
      large HCC patients treated with TACE. Recently, the results of our preliminary pilot study&#xD;
      suggested that, compared with TACE, hepatic arterial infusion chemotherapy (HAIC) may improve&#xD;
      the survivals for HCC with large HCC. Thus, the investigators carried out this prospective&#xD;
      randomized control to demonstrate the superiority of HAIC over TACE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">November 28, 2020</completion_date>
  <primary_completion_date type="Actual">November 28, 2020</primary_completion_date>
  <phase>Phase 3</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>Overall survival</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>30 Days after HAIC</time_frame>
    <description>Postoperative adverse events were graded based on CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of of Patients developed Adverse Events</measure>
    <time_frame>30 Days after HAIC</time_frame>
    <description>Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v3.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">315</enrollment>
  <condition>HepatoCellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Hepatic arterial infusion chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Procedure/Surgery: Hepatic arterial infusion chemotherapy Drug: Folfox Protocol. Hepatic intra-arterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Transarterial chemoembolization</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Procedure/Surgery: Transarterial chemoembolization Drug: TACE Drug Protocol. Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, with or without MMC), and embolization with polyvinyl alcohol particles (PVA).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hepatic arterial infusion chemotherapy</intervention_name>
    <description>A standard hepatic artery catheter was introduced via the femoral artery percutaneously. Selective catheterization of the proper hepatic artery was performed using standard diagnostic catheters and fluoroscopic guidance. In the event of multiple arterial supply(including superior-mesenteric artery), the proportion of the liver supplied by each artery was estimated by the arteriogram. After optimal positioning of the catheter in dominant supplying artery to ensure minimal reflux, the catheter was fixed and connected with infusion tube. In the condition of multiple tumors on both left and right lobe, the gastroduodenal artery was embolized and the catheter was positioned in the hepatic proper artery for infusion. Folfox Protocol were infused through the fixed catheter sequentially.</description>
    <arm_group_label>Hepatic arterial infusion chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transarterial chemoembolization</intervention_name>
    <description>Previous procedure was same with hepatic arterial infusion chemotherapy. After optimal positioning of the catheter, TACE Drug Protocol were injected.</description>
    <arm_group_label>Transarterial chemoembolization</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folfox Protocol</intervention_name>
    <description>oxaliplatin,leucovorin and 5-FU</description>
    <arm_group_label>Hepatic arterial infusion chemotherapy</arm_group_label>
    <other_name>Folfox for TAI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TACE Drug Protocol</intervention_name>
    <description>lipiodol mixed with chemotherapy drugs(EADM , lobaplatin, with or without MMC) followed by polyvinyl alcohol particles (PVA)</description>
    <arm_group_label>Transarterial chemoembolization</arm_group_label>
    <other_name>Drugs for transarterial chemotherapy and embolization</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age range from 18-75 years;&#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;
          -  The sum of diameters of all lesions longer than 10 cm with the maximum lesion longer&#xD;
             than 7 cm.&#xD;
&#xD;
          -  Diagnosed as unresectable with consensus by the panel of liver surgery experts;&#xD;
&#xD;
          -  Re commanded treated by TAI or TACE with consensus by the panel of liver MDT;&#xD;
&#xD;
          -  No past history of TACE, TAI, 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 ≥ 32 g/L;(e) ASL and AST ≤&#xD;
             6 x upper limit of normal;(f) Serum creatinine ≤ 1.5 x upper limit of normal;(g) INR &gt;&#xD;
             2.3 or PT/APTT within normal limits;(h) 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>The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First People's Hospital of Foshan</name>
      <address>
        <city>Foshan</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <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_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/34648352</url>
    <description>Related Info</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 20, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>June 8, 2023</last_update_submitted>
  <last_update_submitted_qc>June 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2023</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>Hepatic arterial infusion chemotherapy</keyword>
  <keyword>Transarterial Chemoembolization</keyword>
  <keyword>BCLC A/B</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>
  <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/NCT02973685
org study id: HCC-S023
nct id: NCT02973685
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion
      chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) in patients with
      large hepatocellular carcinoma staged BCLC A/B.
Transarterial chemoembolization (TACE) is the most widely used palliative treatment for
      hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect of
      TACE for patients with large hepatocellular carcinoma staged BCLC A/B especially for those
      with tumor larger than 10 cm. Our previous prospective study also revealed similar results of
      large HCC patients treated with TACE. Recently, the results of our preliminary pilot study
      suggested that, compared with TACE, hepatic arterial infusion chemotherapy (HAIC) may improve
      the survivals for HCC with large HCC. Thus, the investigators carried out this prospective
      randomized control to demonstrate the superiority of HAIC over TACE.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 24 months
measure: Time to progression
time frame: 24 months
measure: Adverse Events
time frame: 30 Days after HAIC
description: Postoperative adverse events were graded based on CTCAE v4.03
measure: Number of of Patients developed Adverse Events
time frame: 30 Days after HAIC
description: Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v3.0
arm group label: Hepatic arterial infusion chemotherapy
arm group type: Experimental
description: Procedure/Surgery: Hepatic arterial infusion chemotherapy Drug: Folfox Protocol. Hepatic intra-arterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin
arm group label: Transarterial chemoembolization
arm group type: Active Comparator
description: Procedure/Surgery: Transarterial chemoembolization Drug: TACE Drug Protocol. Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, with or without MMC), and embolization with polyvinyl alcohol particles (PVA).
intervention type: Procedure
intervention name: Hepatic arterial infusion chemotherapy
description: A standard hepatic artery catheter was introduced via the femoral artery percutaneously. Selective catheterization of the proper hepatic artery was performed using standard diagnostic catheters and fluoroscopic guidance. In the event of multiple arterial supply(including superior-mesenteric artery), the proportion of the liver supplied by each artery was estimated by the arteriogram. After optimal positioning of the catheter in dominant supplying artery to ensure minimal reflux, the catheter was fixed and connected with infusion tube. In the condition of multiple tumors on both left and right lobe, the gastroduodenal artery was embolized and the catheter was positioned in the hepatic proper artery for infusion. Folfox Protocol were infused through the fixed catheter sequentially.
arm group label: Hepatic arterial infusion chemotherapy
intervention type: Procedure
intervention name: Transarterial chemoembolization
description: Previous procedure was same with hepatic arterial infusion chemotherapy. After optimal positioning of the catheter, TACE Drug Protocol were injected.
arm group label: Transarterial chemoembolization
intervention type: Drug
intervention name: Folfox Protocol
description: oxaliplatin,leucovorin and 5-FU
arm group label: Hepatic arterial infusion chemotherapy
other name: Folfox for TAI
intervention type: Drug
intervention name: TACE Drug Protocol
description: lipiodol mixed with chemotherapy drugs(EADM , lobaplatin, with or without MMC) followed by polyvinyl alcohol particles (PVA)
arm group label: Transarterial chemoembolization
other name: Drugs for transarterial chemotherapy and embolization
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ming Shi, MD
role: Principal Investigator
affiliation: The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center
facility: 
facility: 
facility: 
country: China
url: https://www.ncbi.nlm.nih.gov/pubmed/34648352
description: Related Info
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
sharing ipd: Undecided