<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/NCT02187081</url>
  </required_header>
  <id_info>
    <org_study_id>SWHB008</org_study_id>
    <nct_id>NCT02187081</nct_id>
  </id_info>
  <brief_title>Radiofrequency Ablation Accompanied With Spontaneous Sorafenib in Early to Intermediate Stage HCC</brief_title>
  <official_title>Radiofrequency Ablation Accompanied With Spontaneous Sorafenib Administration in the Treatment of Early to Intermediate Stage Hepatocellular Carcinoma: a Prospective Multicenter Cohort Study.(REASSESS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Southwest Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Southwest Hospital, China</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>
      Radiofrequency ablation (RFA)can be curative with small localized HCCs up to 5 cm in&#xD;
      diameter. However, the long-term prognosis is not satisfactory due to the high incidence of&#xD;
      recurrence.Multimodality treatments are needed to prevent recurrences，but only useful with&#xD;
      locoregional disease. Sorafenib is an oral multi-kinase inhibitor and the only systemic drug&#xD;
      associated with improved overall survival (OS) in patients with advanced HCC. Retrospective&#xD;
      and randomized studies have suggested that the combined use of Sorafenib may be useful in&#xD;
      patients with unresectable HCC. Based on these information and the multiple actions of&#xD;
      Sorafenib, we hypothesized that Sorafenib plus RFA may be useful in patients with early to&#xD;
      Mid term HCC. In this investigation, we evaluated the safety and efficacy of a combination&#xD;
      Sorafenib and RFA therapy in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0 -B1&#xD;
      HCC in a multicenter prospective cohort study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Radiofrequency ablation (RFA) has been used as a minimally invasive option to eradicate&#xD;
      tumors and preserve liver function in patients with impaired function or with a postoperative&#xD;
      tumor recurrence. RFA can be curative with small localized HCCs up to 5 cm in diameter.&#xD;
      However, the long-term prognosis for HCC patients treated with RFA is not satisfactory due to&#xD;
      the high incidence of recurrence including local tumor recurrence and multicentric&#xD;
      carcinogenesis.&#xD;
&#xD;
      Multimodality treatments are needed to prevent recurrences. Although there is a potential&#xD;
      benefit with this strategy, it is only useful with locoregional disease. Sorafenib is an oral&#xD;
      multi-kinase inhibitor and the only systemic drug associated with improved overall survival&#xD;
      (OS) in patients with advanced HCC.&#xD;
&#xD;
      Retrospective and randomized studies have suggested that the combined use of Sorafenib, TACE,&#xD;
      and RFA may be useful in patients with unresectable HCC. Based on these information and the&#xD;
      multiple actions of Sorafenib, we hypothesized that Sorafenib plus RFA may be useful in&#xD;
      patients with early HCC or recurrent HCC. Although no supportive data from clinical trials is&#xD;
      available, this hypothesis is supported by recent animal studies. Inadequate RFA has been&#xD;
      shown to promote rapid progression of residual tumors. Adjuvant Sorafenib postponed time to&#xD;
      recurrence by inhibition of hypoxia inducible factor-1and vascular endothelial growth factor&#xD;
      A (VEGFA). In a multifocal tumor model of HCC, RFA and Sorafenib alone resulted in a&#xD;
      significant volume reduction of non-RFA-targeted tumors, but this effect was enhanced when&#xD;
      both modalities were combined. This phenomenon was also demonstrated by more recent study on&#xD;
      human subject.&#xD;
&#xD;
      Besides the advantages, Sorafenib initially promoted necrosis, delayed tissue repair after&#xD;
      RFA and adversely affected normal liver parenchyma, which could result in increased RFA&#xD;
      toxicity and limit its use in patients with HCC who have undergone RFA. Thus, the overall&#xD;
      advantages of RFA plus Sorafenib need to be weighed against its adverse effects. In this&#xD;
      investigation, we evaluated the safety and efficacy of a combination Sorafenib and RFA&#xD;
      therapy in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0 -B1 HCC in a&#xD;
      multicenter prospective cohort study.&#xD;
&#xD;
      Outcome measures: Post-RFA tumor recurrence&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 15, 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>N/A</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2-year incidence of tumor recurrence</measure>
    <time_frame>2 year</time_frame>
    <description>to calculate the incidence of tumor recurrence of experiment and control group at two year after complete treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-year incidence of recurrence</measure>
    <time_frame>1-year</time_frame>
    <description>1-year incidence of recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3-year incidence of recurrence</measure>
    <time_frame>3 year</time_frame>
    <description>3-year incidence of recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5-year incidence of recurrence</measure>
    <time_frame>5 year</time_frame>
    <description>5-year incidence of recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>average 2 years</time_frame>
    <description>Time to progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate</measure>
    <time_frame>average 2 years</time_frame>
    <description>Disease Control Rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>complications and adverse effect</measure>
    <time_frame>1 year</time_frame>
    <description>to sum all the complications and adverse effect for all the eligible enrolled patients during 1 year of a complete treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">380</enrollment>
  <condition>HCC</condition>
  <arm_group>
    <arm_group_label>Sorafenib+RFA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>We give radiofrequency ablation plus Sorafenib for the treatment of HCC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RFA alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>We give Radiofrequency ablation alone for the treatment of HCC</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>radiofrequency ablation plus Sorafenib</intervention_name>
    <description>To treat HCC with the combination of radiofrequency ablation and sorafenib</description>
    <arm_group_label>Sorafenib+RFA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radiofrequency ablation</intervention_name>
    <description>To treat HCC with radiofrequency ablation alone.</description>
    <arm_group_label>RFA alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Authorization of Informed Consent&#xD;
&#xD;
          -  HCC diagnosed by biopsy or Image findings&#xD;
&#xD;
          -  BCLC stage 0 to B1&#xD;
&#xD;
          -  This time was the primary treatment of HCC. Had no history of any tumor specific&#xD;
             therapy,including RFA,Hepatectomy,TACE,HIFU,and Transplantation&#xD;
&#xD;
          -  Child Pugh A or B&#xD;
&#xD;
          -  ECOG 0 to 2&#xD;
&#xD;
          -  single lesion less than or equal to 5 cm,2 to 3 nodules, maximal size less than equal&#xD;
             to 3cm&#xD;
&#xD;
          -  Male or female (without pregnancy)&#xD;
&#xD;
          -  Ages between 18 to 70 years&#xD;
&#xD;
          -  Capable of take medicines&#xD;
&#xD;
          -  anticipate at least survival of 12 weeks&#xD;
&#xD;
          -  Unwilling to receive surgical resection or liver transplantation&#xD;
&#xD;
          -  Potentially curable disease by RFA&#xD;
&#xD;
          -  Sorafenib administrated less than 4 weeks before or after RFA procedures&#xD;
&#xD;
          -  For any excuse,subject should take Sorafenib at least for 4 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A cancer embolus in major hepatic vessels or extrahepatic metastases&#xD;
&#xD;
          -  Tumor number more than 4 or tumor size larger than 5 cm&#xD;
&#xD;
          -  A present or past history of uncontrollable ascites, hepatic encephalopathy or&#xD;
             variceal bleeding&#xD;
&#xD;
          -  A history of a secondary malignancy&#xD;
&#xD;
          -  Severe dysfunction of the heart, kidney or other organs&#xD;
&#xD;
          -  Active infection except viral hepatitis&#xD;
&#xD;
          -  Any treatment history of target lesion including chemotherapy and TACE&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  received other trials on gene therapy&#xD;
&#xD;
          -  have received operation less than 4 weeks&#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_contact>
    <last_name>Xiaobin Feng, Docter</last_name>
    <phone>86-23-68765297</phone>
    <email>fengxiaobin200708@aliyun.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Southwest Hospital</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400038</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaobin Feng</last_name>
    </contact>
    <investigator>
      <last_name>Kuansheng Ma, Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>July 1, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>March 27, 2017</last_update_submitted>
  <last_update_submitted_qc>March 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Southwest Hospital, China</investigator_affiliation>
    <investigator_full_name>feng xiaobin</investigator_full_name>
    <investigator_title>Dr Xiaobin Feng</investigator_title>
  </responsible_party>
  <keyword>HCC</keyword>
  <keyword>RFA</keyword>
  <keyword>Sorafenib</keyword>
  <keyword>Tumor recurrence</keyword>
  <keyword>Overall survival</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02187081
org study id: SWHB008
nct id: NCT02187081
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Radiofrequency ablation (RFA)can be curative with small localized HCCs up to 5 cm in
      diameter. However, the long-term prognosis is not satisfactory due to the high incidence of
      recurrence.Multimodality treatments are needed to prevent recurrences，but only useful with
      locoregional disease. Sorafenib is an oral multi-kinase inhibitor and the only systemic drug
      associated with improved overall survival (OS) in patients with advanced HCC. Retrospective
      and randomized studies have suggested that the combined use of Sorafenib may be useful in
      patients with unresectable HCC. Based on these information and the multiple actions of
      Sorafenib, we hypothesized that Sorafenib plus RFA may be useful in patients with early to
      Mid term HCC. In this investigation, we evaluated the safety and efficacy of a combination
      Sorafenib and RFA therapy in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0 -B1
      HCC in a multicenter prospective cohort study.
Radiofrequency ablation (RFA) has been used as a minimally invasive option to eradicate
      tumors and preserve liver function in patients with impaired function or with a postoperative
      tumor recurrence. RFA can be curative with small localized HCCs up to 5 cm in diameter.
      However, the long-term prognosis for HCC patients treated with RFA is not satisfactory due to
      the high incidence of recurrence including local tumor recurrence and multicentric
      carcinogenesis.

      Multimodality treatments are needed to prevent recurrences. Although there is a potential
      benefit with this strategy, it is only useful with locoregional disease. Sorafenib is an oral
      multi-kinase inhibitor and the only systemic drug associated with improved overall survival
      (OS) in patients with advanced HCC.

      Retrospective and randomized studies have suggested that the combined use of Sorafenib, TACE,
      and RFA may be useful in patients with unresectable HCC. Based on these information and the
      multiple actions of Sorafenib, we hypothesized that Sorafenib plus RFA may be useful in
      patients with early HCC or recurrent HCC. Although no supportive data from clinical trials is
      available, this hypothesis is supported by recent animal studies. Inadequate RFA has been
      shown to promote rapid progression of residual tumors. Adjuvant Sorafenib postponed time to
      recurrence by inhibition of hypoxia inducible factor-1and vascular endothelial growth factor
      A (VEGFA). In a multifocal tumor model of HCC, RFA and Sorafenib alone resulted in a
      significant volume reduction of non-RFA-targeted tumors, but this effect was enhanced when
      both modalities were combined. This phenomenon was also demonstrated by more recent study on
      human subject.

      Besides the advantages, Sorafenib initially promoted necrosis, delayed tissue repair after
      RFA and adversely affected normal liver parenchyma, which could result in increased RFA
      toxicity and limit its use in patients with HCC who have undergone RFA. Thus, the overall
      advantages of RFA plus Sorafenib need to be weighed against its adverse effects. In this
      investigation, we evaluated the safety and efficacy of a combination Sorafenib and RFA
      therapy in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0 -B1 HCC in a
      multicenter prospective cohort study.

      Outcome measures: Post-RFA tumor recurrence
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: 2-year incidence of tumor recurrence
time frame: 2 year
description: to calculate the incidence of tumor recurrence of experiment and control group at two year after complete treatment.
measure: Overall survival
time frame: 5 years
description: Overall survival
measure: 1-year incidence of recurrence
time frame: 1-year
description: 1-year incidence of recurrence
measure: 3-year incidence of recurrence
time frame: 3 year
description: 3-year incidence of recurrence
measure: 5-year incidence of recurrence
time frame: 5 year
description: 5-year incidence of recurrence
measure: Time to progression
time frame: average 2 years
description: Time to progression
measure: Disease Control Rate
time frame: average 2 years
description: Disease Control Rate
measure: complications and adverse effect
time frame: 1 year
description: to sum all the complications and adverse effect for all the eligible enrolled patients during 1 year of a complete treatment.
arm group label: Sorafenib+RFA
arm group type: Experimental
description: We give radiofrequency ablation plus Sorafenib for the treatment of HCC
arm group label: RFA alone
arm group type: Active Comparator
description: We give Radiofrequency ablation alone for the treatment of HCC
intervention type: Procedure
intervention name: radiofrequency ablation plus Sorafenib
description: To treat HCC with the combination of radiofrequency ablation and sorafenib
arm group label: Sorafenib+RFA
intervention type: Procedure
intervention name: Radiofrequency ablation
description: To treat HCC with radiofrequency ablation alone.
arm group label: RFA alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Xiaobin Feng, Docter
phone: 86-23-68765297
email: fengxiaobin200708@aliyun.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Southwest Hospital, China
investigator full name: feng xiaobin
investigator title: Dr Xiaobin Feng
mesh term: Sorafenib