<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/NCT03775707</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-S063</org_study_id>
    <nct_id>NCT03775707</nct_id>
  </id_info>
  <brief_title>Lenvatinib Plus PD-1 Antibody for Intermediate-stage HCC Beyond Up-to-seven Criteria</brief_title>
  <official_title>Lenvatinib Plus Programmed Cell Death Protein-1 (PD-1) Antibody for Intermediate-stage Hepatocellular Carcinoma Beyond Up-to-seven Criteria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shi Ming</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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 for patients with intermediate-stage hepatocellular carcinoma (HCC) beyond&#xD;
      up-to-seven criteria&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced&#xD;
      hepatocellular carcinoma, and PD-1 antibody was effective and tolerable in patients with&#xD;
      advanced hepatocellular carcinoma. No study has evaluated the efficacy and safety of&#xD;
      lenvatinib plus PD-1 antibody. Thus, the investigators carried out this prospective study to&#xD;
      find out it.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Protocol modification&#xD;
  </why_stopped>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2019</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</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>1</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>
  <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>
  </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>
  </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;
        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>
  <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_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 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>Sponsor-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>Lenvatinib</keyword>
  <keyword>PD-1 Antibody</keyword>
  <keyword>BCLC B stage</keyword>
  <keyword>Beyond up-to-seven criteria</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/NCT03775707
org study id: HCC-S063
nct id: NCT03775707
lead sponsor: 
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 for patients with intermediate-stage hepatocellular carcinoma (HCC) beyond
      up-to-seven criteria
Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced
      hepatocellular carcinoma, and 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. Thus, the investigators carried out this prospective study to
      find out it.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
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: 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.
intervention type: Drug
intervention name: Lenvatinib
description: 12 mg (or 8 mg) once daily (QD) oral dosing.
arm group label: Lenvatinib Plus PD-1
intervention type: Drug
intervention name: PD-1 antibody
description: 3mg/kg intravenously every 2 weeks
arm group label: Lenvatinib Plus PD-1
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Shi Ming
investigator title: Proffessor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Lenvatinib
mesh term: Antibodies