<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/NCT03812770</url>
  </required_header>
  <id_info>
    <org_study_id>HCC-OXA</org_study_id>
    <nct_id>NCT03812770</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of Sorafenib Plus HAIC of FOLFOX vs. Sorafenib Plus HAIC of OXA for Advanced HCC</brief_title>
  <official_title>Sorafenib Plus Hepatic Artery Infusion Chemotherapy of Oxaliplatin, Fluorouracil/Leucovorin Versus Sorafenib Plus Hepatic Artery Infusion Chemotherapy of Oxaliplatin for Advanced Hepatocellular Carcinoma</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>
    <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 hepatic arterial infusion&#xD;
      chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin compared with HAIC of&#xD;
      oxaliplatin alone in patients with advanced hepatocellular carcinoma (HCC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sorafenib is the most widely used palliative treatment for advanced hepatocellular carcinoma&#xD;
      (HCC) patients . Our previous prospective study revealed that sorafenib combined with hepatic&#xD;
      arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin confer a&#xD;
      survival benefit to advanced HCC . However, HAIC of fluorouracil is not such for advanced&#xD;
      HCC. Whether HAIC of oxaliplatin is as effective as HAIC of oxaliplatin plus&#xD;
      fluorouracil/leucovorin is controversial. Thus, the investigators carried out this&#xD;
      prospective randomized control study to find out it.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 4, 2018</start_date>
  <completion_date type="Anticipated">September 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 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>Non-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 (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>
  </primary_outcome>
  <secondary_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>
  </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>30 days</time_frame>
    <description>Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Sorafenib plus HAIC of OXA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sorafenib plus HAIC of FOLFOX</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin, Fluorouracil and Leucovorin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Oral Sorafenib, 400mg, Bid</description>
    <arm_group_label>Sorafenib plus HAIC of FOLFOX</arm_group_label>
    <arm_group_label>Sorafenib plus HAIC of OXA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HAIC of FOLFOX</intervention_name>
    <description>administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries</description>
    <arm_group_label>Sorafenib plus HAIC of FOLFOX</arm_group_label>
    <other_name>Oxaliplatin , fluorouracil, and leucovorin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HAIC of OXA</intervention_name>
    <description>administration of Oxaliplatin via the tumor feeding arteries</description>
    <arm_group_label>Sorafenib plus HAIC of OXA</arm_group_label>
    <other_name>Oxaliplatin</other_name>
  </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 C&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0 to 2&#xD;
&#xD;
          -  with no previous treatment&#xD;
&#xD;
          -  No Cirrhosis or cirrhotic status of Child-Pugh class A only&#xD;
&#xD;
          -  Not amendable to surgical resection ,local ablative therapy and any other cured&#xD;
             treatment.&#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;
&#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;
          -  Any other hemorrhage/bleeding event &gt; CTCAE Grade 3 within 4 weeks of first dose of&#xD;
             study drug&#xD;
&#xD;
          -  Serious non-healing wound, ulcer, or bone fracture&#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>
    <status>Recruiting</status>
    <contact>
      <last_name>Ming Shi</last_name>
      <phone>86-2087343154</phone>
      <phone_ext>86-2087343154</phone_ext>
      <email>shiming@mail.sysu.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Ping Rong, Guo</last_name>
      <phone>86-2087342266</phone>
      <phone_ext>86-2087342266</phone_ext>
      <email>guorongp@mail.sysu.edu.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Ming Shi</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Guangzhou Twelfth People 's Hospita</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510620</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuanmin Zhou, MD</last_name>
      <phone>15521278919</phone>
      <email>13430288977@139.com</email>
    </contact>
    <investigator>
      <last_name>Jinghua Chen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kaiping Central Hospital</name>
      <address>
        <city>Kaiping</city>
        <state>Guangdong</state>
        <zip>529300</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>WanQiang Fang, MD</last_name>
      <phone>13717287622</phone>
      <email>fangwanqiang1970@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 19, 2019</study_first_submitted>
  <study_first_submitted_qc>January 19, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>April 15, 2019</last_update_submitted>
  <last_update_submitted_qc>April 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 17, 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>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>Sorafenib</keyword>
  <keyword>Hepatic artery infusion chemotherapy</keyword>
  <keyword>Oxaliplatin, 5-Fluorouracil and Leucovorin</keyword>
  <keyword>Oxaliplatin</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>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/NCT03812770
org study id: HCC-OXA
nct id: NCT03812770
lead sponsor: 
collaborator: 
collaborator: 
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 hepatic arterial infusion
      chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin compared with HAIC of
      oxaliplatin alone in patients with advanced hepatocellular carcinoma (HCC)
Sorafenib is the most widely used palliative treatment for advanced hepatocellular carcinoma
      (HCC) patients . Our previous prospective study revealed that sorafenib combined with hepatic
      arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin confer a
      survival benefit to advanced HCC . However, HAIC of fluorouracil is not such for advanced
      HCC. Whether HAIC of oxaliplatin is as effective as HAIC of oxaliplatin plus
      fluorouracil/leucovorin is controversial. Thus, the investigators carried out this
      prospective randomized control study to find out it.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
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: 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: 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: 30 days
description: Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03
arm group label: Sorafenib plus HAIC of OXA
arm group type: Experimental
description: Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin
arm group label: Sorafenib plus HAIC of FOLFOX
arm group type: Active Comparator
description: Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin, Fluorouracil and Leucovorin
intervention type: Drug
intervention name: Sorafenib
description: Oral Sorafenib, 400mg, Bid
arm group label: Sorafenib plus HAIC of FOLFOX
arm group label: Sorafenib plus HAIC of OXA
intervention type: Drug
intervention name: HAIC of FOLFOX
description: administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries
arm group label: Sorafenib plus HAIC of FOLFOX
other name: Oxaliplatin , fluorouracil, and leucovorin
intervention type: Drug
intervention name: HAIC of OXA
description: administration of Oxaliplatin via the tumor feeding arteries
arm group label: Sorafenib plus HAIC of OXA
other name: Oxaliplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Shi Ming
investigator title: Clinical Professor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Sorafenib