<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/NCT03791918</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-S065</org_study_id>
    <nct_id>NCT03791918</nct_id>
  </id_info>
  <brief_title>Lenvatinib Plus PD-1 Antibody vs TACE for Intermediate-stage HCC Beyond Up-to-seven Criteria</brief_title>
  <official_title>Lenvatinib Plus Programmed Cell Death Protein-1 (PD-1) Antibody Versus Transarterial Chemoembolization for Intermediate-stage Hepatocellular Carcinoma Beyond Up-to-seven Criteria</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 lenvatinib combined with&#xD;
      PD-1 antibody compared with transarterial chemoembolization (TACE) for patients with&#xD;
      intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria&#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 hepatocellular carcinoma staged BCLC A/B especially for those with&#xD;
      tumor beyond up-to-seven criteria. Recently, Lenvatinib was proved non-inferior to sorafenib&#xD;
      in overall survival in advanced hepatocellular carcinoma, and Programmed Cell Death Protein-1&#xD;
      (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular&#xD;
      carcinoma. No study has evaluated the efficacy and safety of lenvatinib plus PD-1 antibody in&#xD;
      intermediate-stage HCC. Thus, the investigators carried out this prospective randomized&#xD;
      control to demonstrate the superiority of lenvatinib combined with PD-1 antibody over TACE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No participants enrolled&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">January 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2022</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>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Lenvatinib Plus PD-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (&gt;=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (&lt;) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and 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</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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>
  <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>Lenvatinib Plus PD-1</arm_group_label>
    <other_name>E7080, Lenvima</other_name>
  </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>Lenvatinib Plus PD-1</arm_group_label>
    <other_name>Programmed cell death 1 antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>TACE</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. TACE Drug Protocol were injected.</description>
    <arm_group_label>TACE</arm_group_label>
    <other_name>Transarterial chemoembolization</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TACE Drug Protocol</intervention_name>
    <description>lipiodol mixed with chemotherapy drugs(EADM , lobaplatin, and MMC) followed by polyvinyl alcohol particles (PVA)</description>
    <arm_group_label>TACE</arm_group_label>
    <other_name>Drugs for transarterial chemotherapy and embolization</other_name>
  </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 B&#xD;
&#xD;
          -  Beyond up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the&#xD;
             size of the largest tumor [in cm] and the number of tumors)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0 to 1&#xD;
&#xD;
          -  No Cirrhosis or cirrhotic status of Child-Pugh class A only&#xD;
&#xD;
          -  Not applicable for transarterial chemoembolization, surgical resection, and local&#xD;
             ablative therapy.&#xD;
&#xD;
          -  The following laboratory parameters:&#xD;
&#xD;
        Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/ L Serum albumin&#xD;
        ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of&#xD;
        normal INR ≤ 1.5 or PT/APTT 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 1, 2019</study_first_submitted>
  <study_first_submitted_qc>January 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</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>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>Lenvatinib</keyword>
  <keyword>PD-1 Antibody</keyword>
  <keyword>TACE</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>Chlorotrianisene</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/NCT03791918
org study id: HCC-S065
nct id: NCT03791918
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 lenvatinib combined with
      PD-1 antibody compared with transarterial chemoembolization (TACE) for patients with
      intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria
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 hepatocellular carcinoma staged BCLC A/B especially for those with
      tumor beyond up-to-seven criteria. Recently, Lenvatinib was proved non-inferior to sorafenib
      in overall survival in 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 evaluated the efficacy and safety of lenvatinib plus PD-1 antibody in
      intermediate-stage HCC. Thus, the investigators carried out this prospective randomized
      control to demonstrate the superiority of lenvatinib combined with PD-1 antibody 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: 24 months
measure: Progression free survival
time frame: 24 months
arm group label: Lenvatinib Plus PD-1
arm group type: Experimental
description: Participants received lenvatinib capsules 12 milligram (mg) based on the participant's body weight greater than or equal to (>=) 60 kilogram (kg) or 8 mg based on the participant's body weight less than (<) 60 kg at baseline, orally, once daily (QD) in continuous 14-day treatment cycles, and 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
arm group type: Active Comparator
description: Hepatic intra-arterial infusion with lipiodol mixed with chemotherapy drugs (EADM, lobaplatin, and MMC), and embolization with polyvinyl alcohol particles (PVA).
intervention type: Drug
intervention name: Lenvatinib
description: 12 mg (or 8 mg) once daily (QD) oral dosing.
arm group label: Lenvatinib Plus PD-1
other name: E7080, Lenvima
intervention type: Drug
intervention name: PD-1 antibody
description: 3mg/kg intravenously every 2 weeks
arm group label: Lenvatinib Plus PD-1
other name: Programmed cell death 1 antibody
intervention type: Procedure
intervention name: TACE
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. TACE Drug Protocol were injected.
arm group label: TACE
other name: Transarterial chemoembolization
intervention type: Drug
intervention name: TACE Drug Protocol
description: lipiodol mixed with chemotherapy drugs(EADM , lobaplatin, and MMC) followed by polyvinyl alcohol particles (PVA)
arm group label: TACE
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: 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: Chlorotrianisene
mesh term: Antibodies
mesh term: Immunoglobulins