<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/NCT04465734</url>
  </required_header>
  <id_info>
    <org_study_id>HLX10-009-HCC301</org_study_id>
    <nct_id>NCT04465734</nct_id>
  </id_info>
  <brief_title>A Clinical Study to Compare the Efficacy and Safety of HLX10 in Combination With HLX04 Versus Sorafenib as the First-line Treatment in Patients With Locally Advanced or Metastatic HCC</brief_title>
  <official_title>A Randomized, Open-Label, Controlled, Multicenter, Phase III Clinical Study to Compare the Efficacy and Safety of HLX10 (Anti-PD-1 Antibody) in Combination With HLX04 (Anti-VEGF Antibody) Versus Sorafenib as the First-line Treatment in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Henlius Biotech</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Henlius Biotech</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>
      This study is a randomized, double-blind, multicenter, phase III clinical study to compare&#xD;
      the efficacy and safety of HLX10 + HLX04 vs Sorafenibas as the First-line Treatment in&#xD;
      Patients with Locally Advanced or Metastatic HCC&#xD;
&#xD;
      Eligible subjects in this study will be randomized to Arm A or Arm B at 2:1 ratio as follows:&#xD;
&#xD;
      Arm A (treatment group): HLX10 + HLX04 Arm B (control group): sorafenib Randomization is&#xD;
      stratified by: region (Asia (excluding Japan) vs. others), HBV infection vs. HCV infection&#xD;
      vs. no HBV or HCV infection, portal vein invasion or/and extrahepatic spread (with&#xD;
      vs.without), and ECOG (0 vs. 1).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The trial used sorafenib as a control drug. It's not suitable now(after the A+T has been&#xD;
    approved).The sponsor terminated the trial.&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 15, 2022</start_date>
  <completion_date type="Anticipated">March 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 15, 2023</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>tumor assessment</measure>
    <time_frame>defined as a period from randomization to death of the subject for any reason (up to approximately 24 months)</time_frame>
    <description>Overall survival (OS): defined as a period from randomization to death of the subject for any reason.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>tumor assessment</measure>
    <time_frame>Baseline until disease progression or death, whichever occurs first (up to approximately 12 months)</time_frame>
    <description>Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatocellular Carcinoma (HCC)</condition>
  <arm_group>
    <arm_group_label>A (treatment group)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HLX10 in combination with HLX04</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B (control group)</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>sorafenib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HLX10</intervention_name>
    <description>HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.</description>
    <arm_group_label>A (treatment group)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HLX04</intervention_name>
    <description>HLX04 is an recombinant anti-VEGF humanized monoclonal antibody ，developed by Shanghai Henlius Biotech, Inc.</description>
    <arm_group_label>A (treatment group)</arm_group_label>
    <other_name>HLX04 ( anti-VEGF antibody )</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Sorafenib is a multi-target, multi-kinase inhibitor capable.The standard treatment of HCC.</description>
    <arm_group_label>B (control group)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Volunteer to participate in the clinical study;&#xD;
&#xD;
          2. Aged ≥ 18 years and ≤ 75 years;&#xD;
&#xD;
          3. Patients with histopathologically or cytologically diagnosed locally advanced or&#xD;
             metastatic and/or unresectable HCC , or patients with clinically diagnosed HCC&#xD;
             according to the diagnostic criteria of the American Association for the Study of&#xD;
             Liver Diseases (AASLD);&#xD;
&#xD;
          4. Barcelona Clinic Liver Cancer (BCLC) Stage C; or BCLC Stage B patients who are not&#xD;
             candidates for radical surgery and/or locoregional therapy.&#xD;
&#xD;
          5. Received no prior systemic HCC treatment (including chemotherapy, treatment with&#xD;
             sorafenib, regorafenib, lenvatinib, or other small-molecule antiangiogenic agents);&#xD;
&#xD;
          6. At least one measurable lesion by the IRRC (central radiography) as per RECIST v1.1&#xD;
&#xD;
          7. Normal major organ functions as defined&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with known hepatobiliary cell carcinoma, mixed cell carcinoma, or&#xD;
             fibrolamellar cell carcinoma;&#xD;
&#xD;
          2. History of hepatic encephalopathy;&#xD;
&#xD;
          3. Patients with portal hypertension complicated with upper gastrointestinal hemorrhage,&#xD;
             or esophageal/gastric fundal varices with the red color sign, or high hemorrhage risk&#xD;
             investigated by the investigator within 6 months before the randomization. Subjects&#xD;
             must receive endoscopic examinations to rule out high hemorrhage risk (e.g. red color&#xD;
             sign and severe varices) before enrollment.&#xD;
&#xD;
          4. Patients with portal vein invasion at the main portal branch (Vp4), inferior vena cava&#xD;
             involvement, or right cardiac involvement of HCC based on imaging examination.&#xD;
             Patients with portal vein invasion at the main portal branch but with unobstructed&#xD;
             blood flow in the bilateral or unilateral branch can be enrolled;&#xD;
&#xD;
          5. Central nervous system (CNS) or leptomeningeal metastases;&#xD;
&#xD;
          6. Positive for both HBV-DNA and HCV-RNA;&#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>Ethics committee of zhongshan hospital affiliated to fudan university</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>May 1, 2022</last_update_submitted>
  <last_update_submitted_qc>May 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Locally Advanced or Metastatic</keyword>
  <keyword>Hepatocellular Carcinoma (HCC)</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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04465734
org study id: HLX10-009-HCC301
nct id: NCT04465734
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a randomized, double-blind, multicenter, phase III clinical study to compare
      the efficacy and safety of HLX10 + HLX04 vs Sorafenibas as the First-line Treatment in
      Patients with Locally Advanced or Metastatic HCC

      Eligible subjects in this study will be randomized to Arm A or Arm B at 2:1 ratio as follows:

      Arm A (treatment group): HLX10 + HLX04 Arm B (control group): sorafenib Randomization is
      stratified by: region (Asia (excluding Japan) vs. others), HBV infection vs. HCV infection
      vs. no HBV or HCV infection, portal vein invasion or/and extrahepatic spread (with
      vs.without), and ECOG (0 vs. 1).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: tumor assessment
time frame: defined as a period from randomization to death of the subject for any reason (up to approximately 24 months)
description: Overall survival (OS): defined as a period from randomization to death of the subject for any reason.
measure: tumor assessment
time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 12 months)
description: Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
arm group label: A (treatment group)
arm group type: Experimental
description: HLX10 in combination with HLX04
arm group label: B (control group)
arm group type: Sham Comparator
description: sorafenib
intervention type: Drug
intervention name: HLX10
description: HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.
arm group label: A (treatment group)
intervention type: Drug
intervention name: HLX04
description: HLX04 is an recombinant anti-VEGF humanized monoclonal antibody ，developed by Shanghai Henlius Biotech, Inc.
arm group label: A (treatment group)
other name: HLX04 ( anti-VEGF antibody )
intervention type: Drug
intervention name: Sorafenib
description: Sorafenib is a multi-target, multi-kinase inhibitor capable.The standard treatment of HCC.
arm group label: B (control group)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Sorafenib
sharing ipd: No