<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/NCT03289273</url>
  </required_header>
  <id_info>
    <org_study_id>19244</org_study_id>
    <secondary_id>EUPAS20981</secondary_id>
    <nct_id>NCT03289273</nct_id>
  </id_info>
  <brief_title>Observational Study to Evaluate, Under Real-world Practice Conditions, the Safety and Effectiveness of Regorafenib in Patients Diagnosed With Unresectable Hepatocellular Carcinoma (uHCC)</brief_title>
  <official_title>REFINE: Regorafenib Observational Study in Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>No</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>
      Observational study to evaluate, under real-world practice conditions, the safety and&#xD;
      effectiveness of regorafenib in patients diagnosed with unresectable hepatocellular carcinoma&#xD;
      (uHCC)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">June 21, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with treatment emergent adverse events (TEAEs) leading to dose modifications (including reductions, interruptions and permanent discontinuation)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>The primary endpoint is the safety of regorafenib in patients with uHCC, defined as the frequency of documented TEAEs, including serious adverse events (SAEs).&#xD;
Safety will be assessed in all patients who receive at least one dose of regorafenib regardless of prior treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Overall survival (OS) is defined as the time (days) from the start of regorafenib treatment to the date of death, due to any reason. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Progression-free survival (PFS) is defined as the time (days) from the start of regorafenib treatment to the date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Time to progression (TTP) is defined as the time (days) from the start of regorafenib treatment to the first documented disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall tumor response (ORR)</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Best overall tumor response (ORR) will be defined according to investigator-assessed data according to local standard</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of regorafenib treatment</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Duration of regorafenib treatment, defined by the time interval from the start of regorafenib treatment to the day of permanent discontinuation of regorafenib (including death)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1010</enrollment>
  <condition>Liver Neoplasms</condition>
  <arm_group>
    <arm_group_label>uHCC patients treated with regorafenib</arm_group_label>
    <description>Patients with a confirmed diagnosis of uHCC and for whom a decision to treat with regorafenib has been made (by the treating physician)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regorafenib (Stivarga, BAY73-4506)</intervention_name>
    <description>As per the treating physicians discretion</description>
    <arm_group_label>uHCC patients treated with regorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Source population of the study are patients with unresectable hepatocellular carcinoma.&#xD;
        Patients with this condition are mostly managed at specialist centers and cancer hospitals.&#xD;
        The participation of these specialized centers in the study is going to ensure the&#xD;
        representativeness of the study population. Physicians will be asked to sample consecutive&#xD;
        patients whenever possible to avoid selection bias and thus increase the likelihood of&#xD;
        representativeness.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with confirmed diagnosis of unresectable HCC&#xD;
&#xD;
          -  Physician-initiated decision to treat with regorafenib (prior to study enrollment)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in an investigational program with interventions outside of routine&#xD;
             clinical practice&#xD;
&#xD;
          -  Past treatment with regorafenib&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph´s Hospital and Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville - Clinical Trials Unit</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers University</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07101-1709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.R.Wood Cancer Center, Glen Falls Hospital</name>
      <address>
        <city>Glens Falls</city>
        <state>New York</state>
        <zip>12801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinatti</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporal Michael J. Crescenz VA Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Einstein Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Many locations</name>
      <address>
        <city>Multiple Locations</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>China</country>
    <country>Denmark</country>
    <country>Egypt</country>
    <country>France</country>
    <country>Greece</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Russian Federation</country>
    <country>Saudi Arabia</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Albania</country>
    <country>Algeria</country>
    <country>Brazil</country>
    <country>India</country>
    <country>Kazakhstan</country>
    <country>Lebanon</country>
    <country>Luxembourg</country>
    <country>Mexico</country>
    <country>Oman</country>
    <country>United Arab Emirates</country>
  </removed_countries>
  <link>
    <url>http://clinicaltrials.bayer.com/</url>
    <description>Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver cancer</keyword>
  <keyword>unresectable hepatocellular carcinoma</keyword>
  <keyword>real-world practice conditions</keyword>
  <keyword>safety and effectiveness</keyword>
  <keyword>management and treatment of liver cancer</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>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA &quot;Principles for responsible clinical trial data sharing&quot;. This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.</ipd_description>
  </patient_data>
  <!-- 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/NCT03289273
org study id: 19244
secondary id: EUPAS20981
nct id: NCT03289273
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Observational study to evaluate, under real-world practice conditions, the safety and
      effectiveness of regorafenib in patients diagnosed with unresectable hepatocellular carcinoma
      (uHCC)
observational model: Cohort
time perspective: Prospective
measure: Number of patients with treatment emergent adverse events (TEAEs) leading to dose modifications (including reductions, interruptions and permanent discontinuation)
time frame: Up to 24 months
description: The primary endpoint is the safety of regorafenib in patients with uHCC, defined as the frequency of documented TEAEs, including serious adverse events (SAEs).
Safety will be assessed in all patients who receive at least one dose of regorafenib regardless of prior treatment.
measure: Overall survival (OS)
time frame: Up to 24 months
description: Overall survival (OS) is defined as the time (days) from the start of regorafenib treatment to the date of death, due to any reason. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up
measure: Progression-free survival (PFS)
time frame: Up to 24 months
description: Progression-free survival (PFS) is defined as the time (days) from the start of regorafenib treatment to the date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented
measure: Time to progression (TTP)
time frame: Up to 24 months
description: Time to progression (TTP) is defined as the time (days) from the start of regorafenib treatment to the first documented disease progression
measure: Best overall tumor response (ORR)
time frame: Up to 24 months
description: Best overall tumor response (ORR) will be defined according to investigator-assessed data according to local standard
measure: Duration of regorafenib treatment
time frame: Up to 24 months
description: Duration of regorafenib treatment, defined by the time interval from the start of regorafenib treatment to the day of permanent discontinuation of regorafenib (including death)
arm group label: uHCC patients treated with regorafenib
description: Patients with a confirmed diagnosis of uHCC and for whom a decision to treat with regorafenib has been made (by the treating physician)
intervention type: Drug
intervention name: Regorafenib (Stivarga, BAY73-4506)
description: As per the treating physicians discretion
arm group label: uHCC patients treated with regorafenib
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
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country: Argentina
country: Austria
country: Belgium
country: Canada
country: China
country: Denmark
country: Egypt
country: France
country: Greece
country: Italy
country: Japan
country: Korea, Republic of
country: Netherlands
country: Russian Federation
country: Saudi Arabia
country: Spain
country: Sweden
country: Taiwan
country: Thailand
country: Turkey
country: United States
country: Albania
country: Algeria
country: Brazil
country: India
country: Kazakhstan
country: Lebanon
country: Luxembourg
country: Mexico
country: Oman
country: United Arab Emirates
url: http://clinicaltrials.bayer.com/
description: Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Neoplasms
sharing ipd: Undecided
ipd description: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.