xml: <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/NCT05984511</url>
    </required_header>
    <id_info>
      <org_study_id>II2023-162-02</org_study_id>
      <nct_id>NCT05984511</nct_id>
    </id_info>
    <brief_title>TACE Plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy for HCC With Branch PVTT</brief_title>
    <official_title>TACE Plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy for HCC With Branch PVTT: A Phase III, Randomized Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Third Affiliated Hospital, Sun Yat-Sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Sun Yat-sen University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Fifth Affiliated Hospital, Sun Yat-Sen University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Second Affiliated Hospital of Guangzhou Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Maoming People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shandong Provincial Third Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Third Affiliated Hospital, 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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The present study aimed to assess the effectiveness of the combination treatment of&#xD;
        Atezolizumab/Bevacizumab, transcatheter arterial chemoembolization (TACE) and I-125 Seeds&#xD;
        Brachytherapy (TACE-AB-I) in patients with advanced hepatocellular carcinoma (HCC) and portal&#xD;
        vein tumor thrombosis (PVTT). The investigators confirmed that the combination therapy&#xD;
        yielded better survival data than the combined administration of Atezolizumab/Bevacizumab and&#xD;
        TACE (TACE-AB) in patients with advanced HCC and Type I/II PVTT (Based on Cheng's PVTT&#xD;
        classification).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a multicenter, open-label trial, randomized controlled to evaluate the efficacy and&#xD;
        safety of TACE-AB-I compared with TACE-AB for the treatment of HCC with branch PVTT. 234 HCC&#xD;
        patients with branch PVTT will be enrolled in this study. The Patients will be treated with&#xD;
        TACE-AB-I or TACE-AB using a 1:1 randomization scheme. TACE will be performed for the&#xD;
        patients after randomization. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg&#xD;
        bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE and&#xD;
        I-125 Seeds Brachytherapy and last until disease progresses, intolerable toxicity, withdrawal&#xD;
        of informed consent, loss of follow-up, death, or other circumstances that require&#xD;
        termination of treatment, whichever occurs first. For patients in the TACE-AB-I arm,&#xD;
        iodion-125 seeds will be implanted into the PVTT (according to the pre-operative planning)&#xD;
        under CT guidance within 3-7 days after the first TACE. TACE and iodion-125 seeds&#xD;
        implantation can be repeated on demand during follow-up based on the evaluation of laboratory&#xD;
        and imaging examination.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2028</primary_completion_date>
    <phase>N/A</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>
      <intervention_model_description>This is a multicenter, open-label trial, randomized controlled trial to evaluate the efficacy and safety of TACE-AB-I compared with TACE-AB for the treatment of HCC with branch PVTT.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>2 years</time_frame>
      <description>Time from randomization to death from any cause.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression free survival (PFS)</measure>
      <time_frame>2 years</time_frame>
      <description>Time from randomization to disease progression (mRECIST) or death from any cause, whichever occurred first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>2 years</time_frame>
      <description>The percentage of patients who had a best overall tumor response rating of CR and PR (mRECIST).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of portal patency</measure>
      <time_frame>2 years</time_frame>
      <description>The time from randomization until the date that complete portal vein occlusion was confirmed (if the portal vein is patent at diagnosis).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events (AEs)</measure>
      <time_frame>2 years</time_frame>
      <description>Number of patients with AE, treatment-related AE (TRAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">234</enrollment>
    <condition>Hepatocellular Carcinoma</condition>
    <condition>Hepatic Portal Vein Tumor Invasion</condition>
    <condition>Tumor Thrombus</condition>
    <arm_group>
      <arm_group_label>TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>TACE will be performed for the patients after randomization. Iodion-125 seeds will be implanted into the PVTT under CT guidance within 3-7 days after the first TACE.&#xD;
  Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE and I-125 Seeds Brachytherapy.&#xD;
  TACE and iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>TACE and Atezolizumab/Bevacizumab (TACE-AB)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>TACE will be performed for the patients after randomization. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE.&#xD;
  TACE can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>I-125 Seeds Brachytherapy in PVTT</intervention_name>
      <description>Iodine125 seed implantation into the PVTT was conducted 3-7 days after TACE when the results of the liver function tests were comparable to those obtained before TACE. Pre-procedural planning was conducted using a three-dimensional conformal radiation therapy treatment planning system (TPS) to determine the number of Iodine125 seeds required, the target location for implantation, the best percutaneous puncture site and the access route. The targeted zone for implantation was the tumour thrombosis in the segmental portal vein, left/right portal vein. Implantation was guided by CT, and the Iodine125 seeds were implanted into the PVTT using 18 G needles and the implantation gun that housed the Iodine125 seeds in the cartridge chamber.</description>
      <arm_group_label>TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)</arm_group_label>
      <other_name>Iodine-125 Seeds Implantation</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Transcatheter arterial chemoembolization</intervention_name>
      <description>TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE).</description>
      <arm_group_label>TACE and Atezolizumab/Bevacizumab (TACE-AB)</arm_group_label>
      <arm_group_label>TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)</arm_group_label>
      <other_name>TACE</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Atezolizumab plus Bevacizumab</intervention_name>
      <description>Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) .</description>
      <arm_group_label>TACE and Atezolizumab/Bevacizumab (TACE-AB)</arm_group_label>
      <arm_group_label>TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)</arm_group_label>
      <other_name>atezolizumab-bevacizumab; Atez/Bev treatment</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age between18 and 75 years;&#xD;
  &#xD;
            -  Has a diagnosis of HCC confirmed by radiology, histology, or cytology;&#xD;
  &#xD;
            -  Type I PVTT or type II PVTT;&#xD;
  &#xD;
            -  Child-Pugh class A;&#xD;
  &#xD;
            -  Eastern Cooperative Group performance status (ECOG) score of 0-1;&#xD;
  &#xD;
            -  No prior systemic therapy for HCC.&#xD;
  &#xD;
            -  Adequate hematologic and end-organ function;&#xD;
  &#xD;
            -  At least one measurable intrahepatic target lesion.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diffuse HCC;&#xD;
  &#xD;
            -  Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed&#xD;
               hepatocellular/cholangiocarcinoma subtypes (confirmed by histology, or pathology) are&#xD;
               not eligible;&#xD;
  &#xD;
            -  Evidence of extrahepatic spread (EHS);&#xD;
  &#xD;
            -  Any condition representing a contraindication to TACE or I-125 seeds brachytherapy as&#xD;
               determined by the investigators;&#xD;
  &#xD;
            -  Evidence or history of bleeding diathesis or any hemorrhage or bleeding event &gt;CTCAE&#xD;
               grade 3 within 4 weeks prior to randomization;&#xD;
  &#xD;
            -  Active or history of autoimmune disease or immune deficiency;&#xD;
  &#xD;
            -  Untreated or incompletely treated esophageal and/or gastric varices with bleeding or&#xD;
               high risk for bleeding;&#xD;
  &#xD;
            -  A prior bleeding event due to esophageal and/or gastric varices within 6 months prior&#xD;
               to initiation of study treatment;&#xD;
  &#xD;
            -  Evidence of bleeding diathesis or significant coagulopathy;&#xD;
  &#xD;
            -  Pregnant or breastfeeding females;&#xD;
  &#xD;
            -  Significant cardiovascular disease;&#xD;
  &#xD;
            -  Severe infection, such as active tuberculosis;&#xD;
  &#xD;
            -  Serious medical comorbidities;&#xD;
  &#xD;
            -  History of organ or cells transplantation;&#xD;
  &#xD;
            -  History of other uncurable malignancies.&#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>Mingsheng Huang, M.D. &amp; Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mingsheng Huang, M.D. &amp; Ph.D.</last_name>
      <phone>+86-02085253416</phone>
      <email>huangmsh@mail.sysu.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Luwen Mu, M.D.</last_name>
      <phone>+86-13660534361</phone>
      <email>mulw@mail.sysu.edu.cn</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Third Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
      <investigator_full_name>Huang Mingsheng</investigator_full_name>
      <investigator_title>The director of Department of Interventional Radiology</investigator_title>
    </responsible_party>
    <keyword>Hepatocellular Carcinoma (HCC)</keyword>
    <keyword>Portal vein tumor thrombosis (PVTT)</keyword>
    <keyword>Transcatheter arterial chemoembolization (TACE)</keyword>
    <keyword>I-125 Seeds Brachytherapy</keyword>
    <keyword>Atezolizumab plus Bevacizumab</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bevacizumab</mesh_term>
      <mesh_term>Atezolizumab</mesh_term>
      <mesh_term>Antibodies, Monoclonal</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Plan to share IPD with collaborators.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05984511
  org study id: II2023-162-02
  nct id: NCT05984511
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The present study aimed to assess the effectiveness of the combination treatment of
        Atezolizumab/Bevacizumab, transcatheter arterial chemoembolization (TACE) and I-125 Seeds
        Brachytherapy (TACE-AB-I) in patients with advanced hepatocellular carcinoma (HCC) and portal
        vein tumor thrombosis (PVTT). The investigators confirmed that the combination therapy
        yielded better survival data than the combined administration of Atezolizumab/Bevacizumab and
        TACE (TACE-AB) in patients with advanced HCC and Type I/II PVTT (Based on Cheng's PVTT
        classification).
  This is a multicenter, open-label trial, randomized controlled to evaluate the efficacy and
        safety of TACE-AB-I compared with TACE-AB for the treatment of HCC with branch PVTT. 234 HCC
        patients with branch PVTT will be enrolled in this study. The Patients will be treated with
        TACE-AB-I or TACE-AB using a 1:1 randomization scheme. TACE will be performed for the
        patients after randomization. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg
        bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE and
        I-125 Seeds Brachytherapy and last until disease progresses, intolerable toxicity, withdrawal
        of informed consent, loss of follow-up, death, or other circumstances that require
        termination of treatment, whichever occurs first. For patients in the TACE-AB-I arm,
        iodion-125 seeds will be implanted into the PVTT (according to the pre-operative planning)
        under CT guidance within 3-7 days after the first TACE. TACE and iodion-125 seeds
        implantation can be repeated on demand during follow-up based on the evaluation of laboratory
        and imaging examination.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: This is a multicenter, open-label trial, randomized controlled trial to evaluate the efficacy and safety of TACE-AB-I compared with TACE-AB for the treatment of HCC with branch PVTT.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall survival (OS)
  time frame: 2 years
  description: Time from randomization to death from any cause.
  measure: Progression free survival (PFS)
  time frame: 2 years
  description: Time from randomization to disease progression (mRECIST) or death from any cause, whichever occurred first.
  measure: Objective response rate (ORR)
  time frame: 2 years
  description: The percentage of patients who had a best overall tumor response rating of CR and PR (mRECIST).
  measure: Duration of portal patency
  time frame: 2 years
  description: The time from randomization until the date that complete portal vein occlusion was confirmed (if the portal vein is patent at diagnosis).
  measure: Adverse events (AEs)
  time frame: 2 years
  description: Number of patients with AE, treatment-related AE (TRAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0.
  arm group label: TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)
  arm group type: Experimental
  description: TACE will be performed for the patients after randomization. Iodion-125 seeds will be implanted into the PVTT under CT guidance within 3-7 days after the first TACE.
  Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE and I-125 Seeds Brachytherapy.
  TACE and iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.
  arm group label: TACE and Atezolizumab/Bevacizumab (TACE-AB)
  arm group type: Active Comparator
  description: TACE will be performed for the patients after randomization. Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first TACE.
  TACE can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.
  intervention type: Procedure
  intervention name: I-125 Seeds Brachytherapy in PVTT
  description: Iodine125 seed implantation into the PVTT was conducted 3-7 days after TACE when the results of the liver function tests were comparable to those obtained before TACE. Pre-procedural planning was conducted using a three-dimensional conformal radiation therapy treatment planning system (TPS) to determine the number of Iodine125 seeds required, the target location for implantation, the best percutaneous puncture site and the access route. The targeted zone for implantation was the tumour thrombosis in the segmental portal vein, left/right portal vein. Implantation was guided by CT, and the Iodine125 seeds were implanted into the PVTT using 18 G needles and the implantation gun that housed the Iodine125 seeds in the cartridge chamber.
  arm group label: TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)
  other name: Iodine-125 Seeds Implantation
  intervention type: Procedure
  intervention name: Transcatheter arterial chemoembolization
  description: TACE: cTACE (conventional TACE) or dTACE (drug-eluting beads TACE).
  arm group label: TACE and Atezolizumab/Bevacizumab (TACE-AB)
  arm group label: TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)
  other name: TACE
  intervention type: Drug
  intervention name: Atezolizumab plus Bevacizumab
  description: Atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) .
  arm group label: TACE and Atezolizumab/Bevacizumab (TACE-AB)
  arm group label: TACE plus Atezolizumab/Bevacizumab and I-125 Seeds Brachytherapy (TACE-AB-I)
  other name: atezolizumab-bevacizumab; Atez/Bev treatment
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Mingsheng Huang, M.D. & Ph.D.
  role: Principal Investigator
  affiliation: Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University
  last name: Mingsheng Huang, M.D. & Ph.D.
  phone: +86-02085253416
  email: huangmsh@mail.sysu.edu.cn
  last name: Luwen Mu, M.D.
  phone: +86-13660534361
  email: mulw@mail.sysu.edu.cn
  responsible party type: Principal Investigator
  investigator affiliation: Third Affiliated Hospital, Sun Yat-Sen University
  investigator full name: Huang Mingsheng
  investigator title: The director of Department of Interventional Radiology
  mesh term: Carcinoma, Hepatocellular
  mesh term: Bevacizumab
  mesh term: Atezolizumab
  mesh term: Antibodies, Monoclonal
  sharing ipd: No
  ipd description: Plan to share IPD with collaborators.