<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/NCT02220088</url>
  </required_header>
  <id_info>
    <org_study_id>HCC201408</org_study_id>
    <nct_id>NCT02220088</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Retreatment With TAI for Patients Who Showed TACE-resistant: a Randomized Controlled Trial</brief_title>
  <official_title>The Efficacy and Safety of Retreatment With Transcatheter Arterial Infusion (TAI) for Patients Who Showed TACE-resistant: a Randomized Controlled Trial</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Transarterial chemoembolization (TACE) is considered the gold standard for treating&#xD;
      intermediate-stage hepatocellular carcinoma (HCC). However, any treatment guidelines do not&#xD;
      specify the criteria for repeating TACE. The study,conducted in Europe ，recently published in&#xD;
      the journal of Hepatology shows the ART score of &gt;=2.5 prior the second TACE identifies&#xD;
      patients with a dismal prognosis who may not profit from further TACE sessions. However,in&#xD;
      clinical practice，we also found some patients who showed TACE-resistant at the beginning of&#xD;
      treatment may access to get objective response of retreatment with transcatheter arterial&#xD;
      infusion (TAI). So the investigators conduct this prospective,randomized controlled study to&#xD;
      find out whether the patient who showed TACE-resistant can obtain survival benefit from&#xD;
      retreatment with TAI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transarterial chemoembolization (TACE) is considered the gold standard for treating&#xD;
      intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a&#xD;
      heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh&#xD;
      A or B) and disease aetiology.This suggests that not all patients with intermediate-stage HCC&#xD;
      will derive similar benefit from transcatheter arterial infusion (TAI), and that some&#xD;
      patients may benefit from other treatment options.&#xD;
&#xD;
      Repetition of TACE is based on evidence suggesting that one cycle of TACE may not be&#xD;
      sufficient for effective treatment of intermediate-stage HCC and repeating TACE prolongs&#xD;
      survival. However, intermediate-stage HCC patients often have unsatisfactory clinical&#xD;
      outcomes with repeated TACE and there is not sufficiently addressed by existing guidelines&#xD;
      include the criteria for repeating TACE and recommendations about the number of TACE cycles&#xD;
      to be repeated before switching to another or no treatment.The study,recently published in&#xD;
      the journal of Hepatology shows the ART score of &gt;=2.5 prior the second TACE identifies&#xD;
      patients with a dismal prognosis who may not profit from further TACE sessions.In clinical&#xD;
      practice，however, we also found some patients who showed TACE-resistant at the beginning of&#xD;
      treatment may access to get objective response of retreatment with TAI. So we conduct this&#xD;
      prospective,randomized controlled study to find out whether the patient who showed&#xD;
      TACE-resistant can obtain survival benefit from retreatment with TAI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    protocol violation&#xD;
  </why_stopped>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">July 2018</completion_date>
  <primary_completion_date type="Actual">July 2018</primary_completion_date>
  <phase>Phase 2/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>Progression free survival</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events</measure>
    <time_frame>30 days</time_frame>
    <description>All severe adverse events for the entire course of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>TAI of FOLFOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Retreatment With Transcatheter arterial infusion of oxaliplatin , fluorouracil, and leucovorin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sorafenib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>treatment with sorafenib</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>TAI of FOLFOX</intervention_name>
    <description>Retreatment with TAI: administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries</description>
    <arm_group_label>TAI of FOLFOX</arm_group_label>
    <other_name>Transcatheter arterial infusion of oxaliplatin , fluorouracil, and leucovorin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Accept sorafenib.</description>
    <arm_group_label>Sorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients， &gt; 18 years and &lt;=70 years old diagnosed with HCC according to&#xD;
             the European Association for the Study of the Liver (EASL) diagnostic criteria&#xD;
&#xD;
          -  The patient has received 2 session of TACE&#xD;
&#xD;
          -  TACE failure/refractoriness by Liver Cancer Study Group of Japan (LCSGJ) criteria&#xD;
&#xD;
          -  Cirrhotic status of Child-Pugh class A&#xD;
&#xD;
          -  The following laboratory parameters:&#xD;
&#xD;
               -  Platelet count ≥ 60,000/µL&#xD;
&#xD;
               -  Hemoglobin ≥ 8.5 g/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L&#xD;
&#xD;
               -  ASL and AST ≤ 5 x upper limit of normal&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x upper limit of normal&#xD;
&#xD;
               -  INR ≤ 1.5 or PT/APTT within normal limits&#xD;
&#xD;
               -  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;
          -  Patients with complete response (CR) after the first TACE did not receive a further&#xD;
             TACE session&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) &gt;1&#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;
          -  Patients with clinically significant gastrointestinal bleeding within 30 days prior to&#xD;
             study entry.&#xD;
&#xD;
          -  Serious non-healing wound, ulcer, or bone fracture&#xD;
&#xD;
          -  Evidence of bleeding diathesis.&#xD;
&#xD;
          -  Any other hemorrhage/bleeding event &gt; CTCAE Grade 3 within 4 weeks of first dose of&#xD;
             study drug&#xD;
&#xD;
          -  Severe Arterioportal Shunts or Arteriavein Shunts&#xD;
&#xD;
          -  Known metastatic disease&#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>Ming Shi</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Center, Sun Yat-set 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_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, Lencioni R. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2011 May;37(3):212-20. doi: 10.1016/j.ctrv.2010.07.006. Epub 2010 Aug 17.</citation>
    <PMID>20724077</PMID>
  </results_reference>
  <results_reference>
    <citation>Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012 Nov;32(4):348-59. doi: 10.1055/s-0032-1329906. Epub 2013 Feb 8.</citation>
    <PMID>23397536</PMID>
  </results_reference>
  <results_reference>
    <citation>Park JW, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Cheng AL. Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC). Liver Int. 2013 Mar;33(3):327-37. doi: 10.1111/liv.12083. Epub 2013 Jan 18.</citation>
    <PMID>23331661</PMID>
  </results_reference>
  <results_reference>
    <citation>Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Muller C, Heinzl H, Trauner M, Peck-Radosavljevic M. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology. 2013 Jun;57(6):2261-73. doi: 10.1002/hep.26256. Epub 2013 May 3.</citation>
    <PMID>23316013</PMID>
  </results_reference>
  <results_reference>
    <citation>Cheng AL, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Park JW. Re-evaluating transarterial chemoembolization for the treatment of hepatocellular carcinoma: Consensus recommendations and review by an International Expert Panel. Liver Int. 2014 Feb;34(2):174-83. doi: 10.1111/liv.12314. Epub 2013 Nov 20.</citation>
    <PMID>24251922</PMID>
  </results_reference>
  <results_reference>
    <citation>Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Muller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M. The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014 Jan;60(1):118-26. doi: 10.1016/j.jhep.2013.08.022. Epub 2013 Sep 3.</citation>
    <PMID>24012941</PMID>
  </results_reference>
  <results_reference>
    <citation>Yousuf F, Cross TJ, Palmer D. The ART strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014 Jul;61(1):175. doi: 10.1016/j.jhep.2014.02.032. Epub 2014 Mar 18. No abstract available.</citation>
    <PMID>24657396</PMID>
  </results_reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>January 9, 2019</last_update_submitted>
  <last_update_submitted_qc>January 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 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>Prof.</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>TACE</keyword>
  <keyword>TACE failure</keyword>
  <keyword>TACE refractoriness</keyword>
  <keyword>TAI</keyword>
  <keyword>Sorafenib</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>Leucovorin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Sorafenib</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/NCT02220088
org study id: HCC201408
nct id: NCT02220088
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Transarterial chemoembolization (TACE) is considered the gold standard for treating
      intermediate-stage hepatocellular carcinoma (HCC). However, any treatment guidelines do not
      specify the criteria for repeating TACE. The study,conducted in Europe ，recently published in
      the journal of Hepatology shows the ART score of >=2.5 prior the second TACE identifies
      patients with a dismal prognosis who may not profit from further TACE sessions. However,in
      clinical practice，we also found some patients who showed TACE-resistant at the beginning of
      treatment may access to get objective response of retreatment with transcatheter arterial
      infusion (TAI). So the investigators conduct this prospective,randomized controlled study to
      find out whether the patient who showed TACE-resistant can obtain survival benefit from
      retreatment with TAI.
Transarterial chemoembolization (TACE) is considered the gold standard for treating
      intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a
      heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh
      A or B) and disease aetiology.This suggests that not all patients with intermediate-stage HCC
      will derive similar benefit from transcatheter arterial infusion (TAI), and that some
      patients may benefit from other treatment options.

      Repetition of TACE is based on evidence suggesting that one cycle of TACE may not be
      sufficient for effective treatment of intermediate-stage HCC and repeating TACE prolongs
      survival. However, intermediate-stage HCC patients often have unsatisfactory clinical
      outcomes with repeated TACE and there is not sufficiently addressed by existing guidelines
      include the criteria for repeating TACE and recommendations about the number of TACE cycles
      to be repeated before switching to another or no treatment.The study,recently published in
      the journal of Hepatology shows the ART score of >=2.5 prior the second TACE identifies
      patients with a dismal prognosis who may not profit from further TACE sessions.In clinical
      practice，however, we also found some patients who showed TACE-resistant at the beginning of
      treatment may access to get objective response of retreatment with TAI. So we conduct this
      prospective,randomized controlled study to find out whether the patient who showed
      TACE-resistant can obtain survival benefit from retreatment with TAI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: 1 year
measure: Number of Adverse Events
time frame: 30 days
description: All severe adverse events for the entire course of treatment
measure: overall survival
time frame: 1 year
arm group label: TAI of FOLFOX
arm group type: Experimental
description: Retreatment With Transcatheter arterial infusion of oxaliplatin , fluorouracil, and leucovorin
arm group label: Sorafenib
arm group type: Active Comparator
description: treatment with sorafenib
intervention type: Procedure
intervention name: TAI of FOLFOX
description: Retreatment with TAI: administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries
arm group label: TAI of FOLFOX
other name: Transcatheter arterial infusion of oxaliplatin , fluorouracil, and leucovorin
intervention type: Drug
intervention name: Sorafenib
description: Accept sorafenib.
arm group label: Sorafenib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ming Shi
role: Principal Investigator
affiliation: Cancer Center, Sun Yat-set University
facility: 
country: China
citation: Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, Lencioni R. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2011 May;37(3):212-20. doi: 10.1016/j.ctrv.2010.07.006. Epub 2010 Aug 17.
PMID: 20724077
citation: Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012 Nov;32(4):348-59. doi: 10.1055/s-0032-1329906. Epub 2013 Feb 8.
PMID: 23397536
citation: Park JW, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Cheng AL. Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC). Liver Int. 2013 Mar;33(3):327-37. doi: 10.1111/liv.12083. Epub 2013 Jan 18.
PMID: 23331661
citation: Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Muller C, Heinzl H, Trauner M, Peck-Radosavljevic M. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology. 2013 Jun;57(6):2261-73. doi: 10.1002/hep.26256. Epub 2013 May 3.
PMID: 23316013
citation: Cheng AL, Amarapurkar D, Chao Y, Chen PJ, Geschwind JF, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Park JW. Re-evaluating transarterial chemoembolization for the treatment of hepatocellular carcinoma: Consensus recommendations and review by an International Expert Panel. Liver Int. 2014 Feb;34(2):174-83. doi: 10.1111/liv.12314. Epub 2013 Nov 20.
PMID: 24251922
citation: Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Muller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M. The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014 Jan;60(1):118-26. doi: 10.1016/j.jhep.2013.08.022. Epub 2013 Sep 3.
PMID: 24012941
citation: Yousuf F, Cross TJ, Palmer D. The ART strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol. 2014 Jul;61(1):175. doi: 10.1016/j.jhep.2014.02.032. Epub 2014 Mar 18. No abstract available.
PMID: 24657396
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Shi Ming
investigator title: Prof.
mesh term: Carcinoma, Hepatocellular
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Sorafenib