<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/NCT02229071</url>
  </required_header>
  <id_info>
    <org_study_id>ZGDH1B</org_study_id>
    <nct_id>NCT02229071</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Donafenib in Patients With Advanced Hepatocellular Carcinoma</brief_title>
  <official_title>Donafenib in Advanced Hepatocellular Carcinoma: A Randomized Phase 1B Study of Safety, Efficacy, and Pharmacokinetics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tigermed Consulting Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase IB study of donafenib, an oral multikinase inhibitor that targets Raf kinase and&#xD;
      receptor tyrosine kinases, is to assess toxicity,efficacy and pharmacokinetics in patients&#xD;
      wiht advanced hepatocellular carcinoma (HCC) .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligibility Criteria:&#xD;
&#xD;
        -  18 -70 years old;&#xD;
&#xD;
        -  Patients with measurable, histologically proven, inoperable HCC;&#xD;
&#xD;
        -  Child-Pugh (CP) score of A;&#xD;
&#xD;
        -  Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.&#xD;
&#xD;
        -  Patients received prior systemic treatments for HCC before 4 weeks;&#xD;
&#xD;
        -  Patients received operate before 3 months;&#xD;
&#xD;
        -  Patients received TACE before 4 weeks;&#xD;
&#xD;
        -  Life expectancy at least 3 months;&#xD;
&#xD;
        -  Adequate hepatic and renal function;&#xD;
&#xD;
        -  Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per&#xD;
           deciliter);&#xD;
&#xD;
        -  Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or&#xD;
           APTT≤43s;or TT≤21s.&#xD;
&#xD;
      Exclusion Criteria:&#xD;
&#xD;
        -  Patients had prior treatment with sorafenib;&#xD;
&#xD;
        -  CNS involvement.&#xD;
&#xD;
      Method:&#xD;
&#xD;
        -  open-label,randomized,multiceters study;&#xD;
&#xD;
        -  2 dose cohorts: 200mg bid and 300mg bid;&#xD;
&#xD;
        -  Patients with advanced HCC(inoperable) and Child-Pugh (CP) A , randomized,receive&#xD;
           continuous donafenib either 200mg bid or 300mg bid in 4 weeks cycles;&#xD;
&#xD;
        -  Sample size:106 patients(53 patients in each dose cohort).&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
        -  Safety: toxicities are assessed according to CTCAE 3.0;&#xD;
&#xD;
        -  TTP:Tumor response is assessed every two cycles using RECISIT1.1 criteria;&#xD;
&#xD;
        -  Donafenib pharmacokinetics is measured in plasma samples.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">October 30, 2016</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Adverse events</measure>
    <time_frame>1 years</time_frame>
    <description>Patient visits are scheduled every 4 weeks to monitor safety and drug accountability. Patients were monitored for adverse events by use of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to progression(TTP)</measure>
    <time_frame>1 year</time_frame>
    <description>Patient visits are scheduled every 8 weeks to monitor efficacy.TTP is measured from the date of randomisation until disease progression according to RECIST 1.1.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Time to symptomatic progression(TTSP)</measure>
    <time_frame>1 year</time_frame>
    <description>Symtomatic progression is measured with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-HP) domain of physical wellbeing and additional concerns at baseline and every 4 weeks.TTSP is measured from the date of randomisation until symptomatic progression.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>HCC</condition>
  <arm_group>
    <arm_group_label>Donafenib(200mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donafenib 200 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Donafenib(300mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Donafenib 300 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donafenib(200mg)</intervention_name>
    <description>Donafenib 200mg,bid,po</description>
    <arm_group_label>Donafenib(200mg)</arm_group_label>
    <other_name>A Group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donafenib(300mg)</intervention_name>
    <description>Donafenib 300mg,bid,po</description>
    <arm_group_label>Donafenib(300mg)</arm_group_label>
    <other_name>B Group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 -70 years old&#xD;
&#xD;
          -  Patients with measurable, histologically proven, inoperable HCC&#xD;
&#xD;
          -  Child-Pugh (CP) score of A&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.&#xD;
&#xD;
          -  Patients received prior systemic treatments for HCC before 4 weeks&#xD;
&#xD;
          -  Patients received operate before 3 months&#xD;
&#xD;
          -  Patients received TACE before 4 weeks&#xD;
&#xD;
          -  Life expectancy at least 3 months&#xD;
&#xD;
          -  Adequate hepatic and renal function&#xD;
&#xD;
          -  Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per&#xD;
             deciliter)&#xD;
&#xD;
          -  Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or&#xD;
             APTT≤43s;or TT≤21s.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients had prior treatment with sorafenib&#xD;
&#xD;
          -  CNS involvement.&#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>Feng Bi, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sichuan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West China Hospital,SCU</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <last_update_submitted>March 20, 2019</last_update_submitted>
  <last_update_submitted_qc>March 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Donafenib</keyword>
  <keyword>HCC</keyword>
  <keyword>Advanced</keyword>
  <keyword>inoperable</keyword>
  <keyword>Phase 1B</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_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/NCT02229071
org study id: ZGDH1B
nct id: NCT02229071
lead sponsor: 
collaborator: 
has dmc: No
This phase IB study of donafenib, an oral multikinase inhibitor that targets Raf kinase and
      receptor tyrosine kinases, is to assess toxicity,efficacy and pharmacokinetics in patients
      wiht advanced hepatocellular carcinoma (HCC) .
Eligibility Criteria:

        -  18 -70 years old;

        -  Patients with measurable, histologically proven, inoperable HCC;

        -  Child-Pugh (CP) score of A;

        -  Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.

        -  Patients received prior systemic treatments for HCC before 4 weeks;

        -  Patients received operate before 3 months;

        -  Patients received TACE before 4 weeks;

        -  Life expectancy at least 3 months;

        -  Adequate hepatic and renal function;

        -  Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per
           deciliter);

        -  Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or
           APTT≤43s;or TT≤21s.

      Exclusion Criteria:

        -  Patients had prior treatment with sorafenib;

        -  CNS involvement.

      Method:

        -  open-label,randomized,multiceters study;

        -  2 dose cohorts: 200mg bid and 300mg bid;

        -  Patients with advanced HCC(inoperable) and Child-Pugh (CP) A , randomized,receive
           continuous donafenib either 200mg bid or 300mg bid in 4 weeks cycles;

        -  Sample size:106 patients(53 patients in each dose cohort).

      Endpoints:

        -  Safety: toxicities are assessed according to CTCAE 3.0;

        -  TTP:Tumor response is assessed every two cycles using RECISIT1.1 criteria;

        -  Donafenib pharmacokinetics is measured in plasma samples.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events
time frame: 1 years
description: Patient visits are scheduled every 4 weeks to monitor safety and drug accountability. Patients were monitored for adverse events by use of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0
measure: Time to progression(TTP)
time frame: 1 year
description: Patient visits are scheduled every 8 weeks to monitor efficacy.TTP is measured from the date of randomisation until disease progression according to RECIST 1.1.
measure: Time to symptomatic progression(TTSP)
time frame: 1 year
description: Symtomatic progression is measured with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-HP) domain of physical wellbeing and additional concerns at baseline and every 4 weeks.TTSP is measured from the date of randomisation until symptomatic progression.
arm group label: Donafenib(200mg)
arm group type: Experimental
description: Donafenib 200 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
arm group label: Donafenib(300mg)
arm group type: Active Comparator
description: Donafenib 300 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
intervention type: Drug
intervention name: Donafenib(200mg)
description: Donafenib 200mg,bid,po
arm group label: Donafenib(200mg)
other name: A Group
intervention type: Drug
intervention name: Donafenib(300mg)
description: Donafenib 300mg,bid,po
arm group label: Donafenib(300mg)
other name: B Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Feng Bi, Doctor
role: Principal Investigator
affiliation: Sichuan University
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular