<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/NCT02971345</url>
  </required_header>
  <id_info>
    <org_study_id>ZS-IR-2016</org_study_id>
    <nct_id>NCT02971345</nct_id>
  </id_info>
  <brief_title>Endovascular Brachytherapy Combined With Stent Placement and TACE for HCC With Main Portal Vein Tumor Thrombus</brief_title>
  <official_title>Endovascular Brachytherapy Combined With Stent Placement and Transcatheter Arterial Chemoembolization (TACE) for Treatment of HCC With Main Portal Vein Tumor Thrombus Versus TACE Alone: a Prospective Randomized Controlled Multicentre Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Zhongshan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lishui Country People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Changhai Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Anhui Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Second People's Hospital of Yibin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Shanxi Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>LanZhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Hospital of China Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fujian Medical University Union Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fujian Provincial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wuhan Union Hospital, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ZhuHai Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhongshan Hospital Xiamen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Yancheng Third People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Changzhou Wujin People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tengzhou Central People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Harbin Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hunan Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Zhongshan Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is a prospective and multi-center clinical research in China to compare the efficacy,&#xD;
      safety and related impact factors between TACE alone and endovascular brachytherapy combined&#xD;
      with stent placement and TACE for HCC with main portal vein tumor thrombus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is an open random prospective phase III clinical trial conducted by Principal Investigator&#xD;
      Professor Zhi-ping Yan.Investigators in twenty-seven hospitals in China participate&#xD;
      in.Patients with unresectable HCC with main portal vein tumor thrombus are enrolled. The&#xD;
      investigators propose to recruitment 253 patients who are randomly assigned into the combined&#xD;
      group (treated with endovascular brachytherapy combined with stent placement and TACE) and&#xD;
      the control group (treated with TACE alone).There are 127 patients in combined group and 126&#xD;
      patients in control group. The criteria of inclusion and exclusion, and the methods of lab&#xD;
      tests, imaging modality and treatment procedures are the same.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">November 2020</completion_date>
  <primary_completion_date type="Anticipated">October 2020</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>From the date of randomization until the date of death from any cause, assessed up to 24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time To Progression</measure>
    <time_frame>From the date of first procedure of TACE or combined therapy until the time when the disease progresses from an intermediate to an advanced stage as defined by specific events, assessed up to 24 months</time_frame>
    <description>Time to progression follow-up is done at three months interval after lesions defined as stable with treatment of TACE or combined therapy six months after enrollment until lesions are defined as disease progression.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">253</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Portal Vein Tumor Thrombus</condition>
  <arm_group>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transarterial chemoembolization (TACE) is performed immediately following Iodine-125 seed strand and stent implantation.&#xD;
Epirubicin,ultra-fluid lipiodol and gelatin sponge articles are used in TACE.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TACE alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Only TACE is performed. Epirubicin, ultra-fluid lipiodol and gelatin sponge articles are used in TACE.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Stent and Iodine-125 seed strand implantation</intervention_name>
    <description>The patent second-order branch of the intrahepatic portal vein was punctured with a 22-gauge Chiba needle under ultrasound guidance.Stent and Iodine-125 seed strand are implanted by two 0.035-inch,150-cm-long wire.</description>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Stent</intervention_name>
    <description>Bare stent should be placed through a 7-F, 23-cm-long sheath over the wire.</description>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Iodine-125 seed</intervention_name>
    <description>The number of Iodine-125 seeds planned to be implanted was calculated by the following formula: N = length of obstructed main portal vein (mm)/4.5 + 4. These seeds were arranged linearly and sealed into a 4-F catheter continuously to construct a Iodine-125 seed strand.</description>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>Epirubicin is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: Epirubicin 30-60 mg per patient,depending on the situation of the patient.</description>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
    <arm_group_label>TACE alone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ultra-fluid lipiodol</intervention_name>
    <description>Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .</description>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
    <arm_group_label>TACE alone</arm_group_label>
    <other_name>lipiodol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Gelatin sponge articles</intervention_name>
    <description>Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.</description>
    <arm_group_label>Endovascular Brachytherapy&amp;Stent&amp;TACE</arm_group_label>
    <arm_group_label>TACE alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  (1) Hepatocellular carcinoma(HCC) diagnosis confirmed by needle biopsy or by two&#xD;
             coincidental imaging techniques associated with increased α-fetoprotein according to&#xD;
             the American Association for the Study of Liver Diseases (AASLD) guidelines;&#xD;
&#xD;
          -  (2) According to the Barcelona Clinic Liver Cancer staging classification, HCC was&#xD;
             unsuitable for resection, liver transplantation or percutaneous radiofrequency&#xD;
             ablation;&#xD;
&#xD;
          -  (3) Tumor thrombus, a low-attenuation intraluminal filling defect extending from&#xD;
             intrahepatic portal vein branches adjacent to primary tumor into main portal vein, was&#xD;
             confirmed by contrast-enhanced abdominal computer tomography (CT) or magnetic&#xD;
             resonance imaging (MRI)&#xD;
&#xD;
          -  (4) At least the first-order branch of the intrahepatic portal vein was patent in one&#xD;
             lobe;&#xD;
&#xD;
          -  (5) Child-Pugh classification grade A or B;&#xD;
&#xD;
          -  (6) Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (1) Patients had a history of any therapy for HCC or portal vein tumor thrombus;&#xD;
&#xD;
          -  (2) Advanced liver disease (bilirubin levels &gt;3 mg/dL, Aspartate transaminase or&#xD;
             Alanine aminotransferase &gt;5 × upper limit of normal)；&#xD;
&#xD;
          -  (3) Tumor invade the Inferior Vena Cava, extrahepatic spread;&#xD;
&#xD;
          -  (4) Any contraindication to an arterial procedure such as impaired clotting tests&#xD;
             (platelet count below 50 × 109/L or prothrombin activity below 50 %);&#xD;
&#xD;
          -  (5) Renal failure,cardiac ejection fraction (&lt;50 %) or end-stage disease;&#xD;
&#xD;
          -  (6) Patients who were not capable of cooperation during the procedure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhiping Yan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Interventional Radiology, Zhongshan Hospital, Fudan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jianjun Luo, MD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Interventional Radiology, Zhongshan Hospital, Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zihan Zhang, MD</last_name>
    <phone>+8615901785843</phone>
    <email>zhangzihan0217@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wen Zhang, MD</last_name>
    <phone>+8613774267409</phone>
    <email>wenzhangxiao@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Interventional Radiology, Zhongshan Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jianjun Luo, MD</last_name>
      <email>zhangzihan0217@126.com</email>
    </contact>
    <investigator>
      <last_name>Zhinping Yan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jianjun Luo, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Luo J, Yan Z, Liu Q, Qu X, Wang J. Endovascular placement of iodine-125 seed strand and stent combined with chemoembolization for treatment of hepatocellular carcinoma with tumor thrombus in main portal vein. J Vasc Interv Radiol. 2011 Apr;22(4):479-89. doi: 10.1016/j.jvir.2010.11.029.</citation>
    <PMID>21463757</PMID>
  </results_reference>
  <results_reference>
    <citation>Luo JJ, Zhang ZH, Liu QX, Zhang W, Wang JH, Yan ZP. Endovascular brachytherapy combined with stent placement and TACE for treatment of HCC with main portal vein tumor thrombus. Hepatol Int. 2016 Jan;10(1):185-95. doi: 10.1007/s12072-015-9663-8. Epub 2015 Sep 4.</citation>
    <PMID>26341514</PMID>
  </results_reference>
  <results_reference>
    <citation>Yang M, Fang Z, Yan Z, Luo J, Liu L, Zhang W, Wu L, Ma J, Yang Q, Liu Q. Transarterial chemoembolisation (TACE) combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone: a two-arm, randomised clinical trial. J Cancer Res Clin Oncol. 2014 Feb;140(2):211-9. doi: 10.1007/s00432-013-1568-0. Epub 2013 Dec 28. Erratum In: J Cancer Res Clin Oncol. 2014 Apr;140(4):687-8.</citation>
    <PMID>24374800</PMID>
  </results_reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>November 20, 2016</study_first_submitted>
  <study_first_submitted_qc>November 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>June 9, 2020</last_update_submitted>
  <last_update_submitted_qc>June 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>main portal vein tumor thrombus</keyword>
  <keyword>endovascular brachytherapy</keyword>
  <keyword>stent</keyword>
  <keyword>chemoembolization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iodine</mesh_term>
    <mesh_term>Cadexomer iodine</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Ethiodized Oil</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/NCT02971345
org study id: ZS-IR-2016
nct id: NCT02971345
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has dmc: No
It is a prospective and multi-center clinical research in China to compare the efficacy,
      safety and related impact factors between TACE alone and endovascular brachytherapy combined
      with stent placement and TACE for HCC with main portal vein tumor thrombus.
It is an open random prospective phase III clinical trial conducted by Principal Investigator
      Professor Zhi-ping Yan.Investigators in twenty-seven hospitals in China participate
      in.Patients with unresectable HCC with main portal vein tumor thrombus are enrolled. The
      investigators propose to recruitment 253 patients who are randomly assigned into the combined
      group (treated with endovascular brachytherapy combined with stent placement and TACE) and
      the control group (treated with TACE alone).There are 127 patients in combined group and 126
      patients in control group. The criteria of inclusion and exclusion, and the methods of lab
      tests, imaging modality and treatment procedures are the same.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival
time frame: From the date of randomization until the date of death from any cause, assessed up to 24 months
measure: Time To Progression
time frame: From the date of first procedure of TACE or combined therapy until the time when the disease progresses from an intermediate to an advanced stage as defined by specific events, assessed up to 24 months
description: Time to progression follow-up is done at three months interval after lesions defined as stable with treatment of TACE or combined therapy six months after enrollment until lesions are defined as disease progression.
arm group label: Endovascular Brachytherapy&Stent&TACE
arm group type: Experimental
description: Transarterial chemoembolization (TACE) is performed immediately following Iodine-125 seed strand and stent implantation.
Epirubicin,ultra-fluid lipiodol and gelatin sponge articles are used in TACE.
arm group label: TACE alone
arm group type: Active Comparator
description: Only TACE is performed. Epirubicin, ultra-fluid lipiodol and gelatin sponge articles are used in TACE.
intervention type: Procedure
intervention name: Stent and Iodine-125 seed strand implantation
description: The patent second-order branch of the intrahepatic portal vein was punctured with a 22-gauge Chiba needle under ultrasound guidance.Stent and Iodine-125 seed strand are implanted by two 0.035-inch,150-cm-long wire.
arm group label: Endovascular Brachytherapy&Stent&TACE
intervention type: Device
intervention name: Stent
description: Bare stent should be placed through a 7-F, 23-cm-long sheath over the wire.
arm group label: Endovascular Brachytherapy&Stent&TACE
intervention type: Device
intervention name: Iodine-125 seed
description: The number of Iodine-125 seeds planned to be implanted was calculated by the following formula: N = length of obstructed main portal vein (mm)/4.5 + 4. These seeds were arranged linearly and sealed into a 4-F catheter continuously to construct a Iodine-125 seed strand.
arm group label: Endovascular Brachytherapy&Stent&TACE
intervention type: Drug
intervention name: Epirubicin
description: Epirubicin is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: Epirubicin 30-60 mg per patient,depending on the situation of the patient.
arm group label: Endovascular Brachytherapy&Stent&TACE
arm group label: TACE alone
intervention type: Drug
intervention name: Ultra-fluid lipiodol
description: Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .
arm group label: Endovascular Brachytherapy&Stent&TACE
arm group label: TACE alone
other name: lipiodol
intervention type: Other
intervention name: Gelatin sponge articles
description: Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.
arm group label: Endovascular Brachytherapy&Stent&TACE
arm group label: TACE alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Zhiping Yan, MD
role: Principal Investigator
affiliation: Department of Interventional Radiology, Zhongshan Hospital, Fudan University
last name: Jianjun Luo, MD
role: Study Director
affiliation: Department of Interventional Radiology, Zhongshan Hospital, Fudan University
last name: Zihan Zhang, MD
phone: +8615901785843
email: zhangzihan0217@126.com
last name: Wen Zhang, MD
phone: +8613774267409
email: wenzhangxiao@126.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
citation: Luo J, Yan Z, Liu Q, Qu X, Wang J. Endovascular placement of iodine-125 seed strand and stent combined with chemoembolization for treatment of hepatocellular carcinoma with tumor thrombus in main portal vein. J Vasc Interv Radiol. 2011 Apr;22(4):479-89. doi: 10.1016/j.jvir.2010.11.029.
PMID: 21463757
citation: Luo JJ, Zhang ZH, Liu QX, Zhang W, Wang JH, Yan ZP. Endovascular brachytherapy combined with stent placement and TACE for treatment of HCC with main portal vein tumor thrombus. Hepatol Int. 2016 Jan;10(1):185-95. doi: 10.1007/s12072-015-9663-8. Epub 2015 Sep 4.
PMID: 26341514
citation: Yang M, Fang Z, Yan Z, Luo J, Liu L, Zhang W, Wu L, Ma J, Yang Q, Liu Q. Transarterial chemoembolisation (TACE) combined with endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus TACE alone: a two-arm, randomised clinical trial. J Cancer Res Clin Oncol. 2014 Feb;140(2):211-9. doi: 10.1007/s00432-013-1568-0. Epub 2013 Dec 28. Erratum In: J Cancer Res Clin Oncol. 2014 Apr;140(4):687-8.
PMID: 24374800
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular
mesh term: Thrombosis
mesh term: Iodine
mesh term: Cadexomer iodine
mesh term: Epirubicin
mesh term: Ethiodized Oil