<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/NCT03803254</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-S058</org_study_id>
    <nct_id>NCT03803254</nct_id>
  </id_info>
  <brief_title>HAIC Plus Lenvatinib and PD-1 Antibody Versus HAIC Plus Lenvatinib for Advanced HCC</brief_title>
  <official_title>Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Programmed Cell Death Protein-1 Antibody Versus Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib 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 arterial infusion&#xD;
      chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and programmed&#xD;
      cell death protein-1 antibody compared with lenvtinib Alone in patients with hepatic arterial&#xD;
      infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib for&#xD;
      advanced hepatocellular carcinoma (HCC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin&#xD;
      was effective and safe for hepatocellular carcinoma. Lenvatinib was non-inferior to sorafenib&#xD;
      in overall survival in untreated advanced hepatocellular carcinoma, and programmed cell death&#xD;
      protein-1 (PD-1) antibody was effective and tolerable in patients with advanced&#xD;
      hepatocellular carcinoma. No study has compared HAIC plus lenvatinib and PD-1 antibody with&#xD;
      HAIC plus lenvatinib. Thus, the investigators carried out this prospective randomized control&#xD;
      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">January 3, 2019</start_date>
  <completion_date type="Anticipated">January 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2021</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>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>
  </primary_outcome>
  <secondary_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>
  </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>HAIC plus lenvatinib and PD-1 antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hepatic arterial infusion chemotherapy plus lenvatinib and programmed cell death protein-1 antibody</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HAIC plus lenvatinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hepatic arterial infusion chemotherapy plus lenvatinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hepatic arterial infusion chemotherapy</intervention_name>
    <description>administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries</description>
    <arm_group_label>HAIC plus lenvatinib</arm_group_label>
    <arm_group_label>HAIC plus lenvatinib and PD-1 antibody</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folfox Protocol</intervention_name>
    <description>Oxaliplatin , fluorouracil, and leucovorin</description>
    <arm_group_label>HAIC plus lenvatinib</arm_group_label>
    <arm_group_label>HAIC plus lenvatinib and PD-1 antibody</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenvatinib</intervention_name>
    <description>12 mg (or 8 mg) once daily (QD) oral dosing.</description>
    <arm_group_label>HAIC plus lenvatinib</arm_group_label>
    <arm_group_label>HAIC plus lenvatinib and 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>HAIC plus lenvatinib and PD-1 antibody</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;
          -  Eastern Cooperative Oncology Group performance status of 0 to 2&#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;
        Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x&#xD;
        upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT&#xD;
        within normal limits 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 Hospita</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>January 2019</verification_date>
  <study_first_submitted>January 11, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</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>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>Lenvatinib</keyword>
  <keyword>PD-1 Antibody</keyword>
  <keyword>Oxaliplatin, 5-Fluorouracil and Leucovorin</keyword>
  <keyword>Hepatic arterial infusion chemotherapy</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>Lenvatinib</mesh_term>
    <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/NCT03803254
org study id: HCC-S058
nct id: NCT03803254
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 arterial infusion
      chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and programmed
      cell death protein-1 antibody compared with lenvtinib Alone in patients with hepatic arterial
      infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib for
      advanced hepatocellular carcinoma (HCC)
Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin
      was effective and safe for hepatocellular carcinoma. Lenvatinib was non-inferior to sorafenib
      in overall survival in untreated advanced hepatocellular carcinoma, and programmed cell death
      protein-1 (PD-1) antibody was effective and tolerable in patients with advanced
      hepatocellular carcinoma. No study has compared HAIC plus lenvatinib and PD-1 antibody with
      HAIC plus lenvatinib. 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: 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: 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: 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: HAIC plus lenvatinib and PD-1 antibody
arm group type: Experimental
description: Hepatic arterial infusion chemotherapy plus lenvatinib and programmed cell death protein-1 antibody
arm group label: HAIC plus lenvatinib
arm group type: Active Comparator
description: Hepatic arterial infusion chemotherapy plus lenvatinib
intervention type: Procedure
intervention name: Hepatic arterial infusion chemotherapy
description: administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries
arm group label: HAIC plus lenvatinib
arm group label: HAIC plus lenvatinib and PD-1 antibody
intervention type: Drug
intervention name: Folfox Protocol
description: Oxaliplatin , fluorouracil, and leucovorin
arm group label: HAIC plus lenvatinib
arm group label: HAIC plus lenvatinib and PD-1 antibody
intervention type: Drug
intervention name: Lenvatinib
description: 12 mg (or 8 mg) once daily (QD) oral dosing.
arm group label: HAIC plus lenvatinib
arm group label: HAIC plus lenvatinib and PD-1 antibody
intervention type: Drug
intervention name: PD-1 antibody
description: 3mg/kg intravenously every 2 weeks
arm group label: HAIC plus lenvatinib and PD-1 antibody
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: Clinical Professor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Lenvatinib
mesh term: Antibodies