<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/NCT01714609</url>
  </required_header>
  <id_info>
    <org_study_id>1002006266</org_study_id>
    <nct_id>NCT01714609</nct_id>
  </id_info>
  <brief_title>The Effect of Sorafenib on Portal Pressure</brief_title>
  <official_title>A Multi-Center, Placebo-Controlled Randomized Pilot of the Effect of Sorafenib on Portal Pressure in Patients With Cirrhosis, Portal Hypertension and Hepatocellular Carcinoma Treated With Ablative Therapy and/or Transarterial Chemoembolization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Onyx Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sorafenib is approved by the US FDA for the treatment of unresectable (can not operate) liver&#xD;
      cancer and for renal cell carcinoma. Sorafenib is a drug that inhibits the growth of cancer&#xD;
      cells and prevents the formation of new blood vessels that would otherwise help the cancer&#xD;
      spread.&#xD;
&#xD;
      Studies in experimental animals have shown that sorafenib may also lower portal vein pressure&#xD;
      (the pressure of the blood passing from the intestine through the liver.) This study seeks to&#xD;
      determine if sorafenib lowers the blood pressure in liver blood vessels (portal vein&#xD;
      pressure) in patients with cirrhosis who have high portal vein pressure. The study will also&#xD;
      obtain information whether sorafenib is safe in this patient population.&#xD;
&#xD;
      Half of the patients will be given sorafenib and half will be given a placebo (a pill without&#xD;
      any medicine in it.) This allows a comparison of the reactions of people who take sorafenib&#xD;
      to those who do not.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot proof-of-concept study that investigates the effect of sorafenib on portal&#xD;
      pressure, as determined by the hepatic venous pressure gradient (HVPG), in patients with&#xD;
      liver cirrhosis, portal hypertension and unresectable hepatocellular carcinoma (HCC) that has&#xD;
      successfully responded to radiofrequency ablation and/or transarterial chemoembolization, and&#xD;
      have obtained a complete response.&#xD;
&#xD;
      The primary end-point of the study is the change in HVPG observed from baseline to three&#xD;
      months after starting treatment with sorafenib. Secondary end-point is safety of sorafenib.&#xD;
&#xD;
      The trial is structured as a randomized double blind placebo controlled study. After a&#xD;
      three-month period of therapy with sorafenib or placebo (double-blind phase), patients will&#xD;
      be given open-label sorafenib for an additional 3-month period (open-label phase). A total of&#xD;
      44 patients will be randomized (in the initial phase) on a 1:1 ratio to sorafenib or placebo.&#xD;
      Patients will be followed monthly and HCC follow-up will be according to standards of care.&#xD;
      The study will be sponsored by Onyx, who will also provide the treatment medication&#xD;
      (sorafenib and placebo)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Patients With Change in HVPG From Baseline</measure>
    <time_frame>Three Months</time_frame>
    <description>Number of participants with a decrease in HPVG that was &gt; 10% of baseline</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Clinically Significant Portal Hypertension</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sorafenib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo Comparator: Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Sorafenib, 400 mg twice daily</description>
    <arm_group_label>Sorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Age 20-75 years&#xD;
&#xD;
          -  Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver,&#xD;
             splenomegaly and/or collaterals&#xD;
&#xD;
          -  HCC proven histologically or diagnosed following the AASLD criteria if biopsy not&#xD;
             feasible or refused by the patient&#xD;
&#xD;
          -  HCC must be unresectable and within UCSF criteria (single tumor ≤ 6.5 cm diameter, or,&#xD;
             if multiple lesions, maximum diameter of the largest lesion ≤ 4.5 and total tumor&#xD;
             diameter ≤ 8 cm (23))&#xD;
&#xD;
          -  CPT score &lt;9 (that is all Child A and Child B with a score of 7 or 8)&#xD;
&#xD;
          -  Complete response to treatment with RFA (including that performed laparoscopically) or&#xD;
             TACE or a combination of the above as defined by radiologic criteria (hepatoma&#xD;
             protocol MRI or CT scan performed 4-6 weeks after the procedure).&#xD;
&#xD;
          -  No more than two ablative procedures prior to enrollment&#xD;
&#xD;
          -  Presence of portal hypertension, as defined by HVPG of &gt;5 mmHg&#xD;
&#xD;
          -  EGD for variceal screening performed within 6 months of entry into the study unless&#xD;
             the patient is already on a stable dose of a non selective beta-blocker (adjusted to&#xD;
             obtain a heart rate of 55-60 bpm) or treated with variceal band ligation.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test performed&#xD;
             within 7 days prior to the start of treatment&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             (barrier method of birth control) prior to study entry and for the duration of study&#xD;
             participation. Men should use adequate birth control for at least three months after&#xD;
             the last administration of sorafenib.&#xD;
&#xD;
          -  Signed informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guadalupe Garcia-Tsao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Medical Center West Haven</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham &amp; Womens</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania School of Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>October 23, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 26, 2012</study_first_posted>
  <results_first_submitted>November 3, 2015</results_first_submitted>
  <results_first_submitted_qc>November 3, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 9, 2015</results_first_posted>
  <last_update_submitted>December 2, 2020</last_update_submitted>
  <last_update_submitted_qc>December 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>portal hypertension</keyword>
  <keyword>sorafenib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Portal</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.&#xD;
Placebo: Placebo Comparator: Placebo</description>
        </group>
        <group group_id="P2">
          <title>Sorafenib</title>
          <description>Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.&#xD;
Sorafenib: Sorafenib, 400 mg twice daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.&#xD;
Placebo: Placebo Comparator: Placebo</description>
        </group>
        <group group_id="B2">
          <title>Sorafenib</title>
          <description>Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.&#xD;
Sorafenib: Sorafenib, 400 mg twice daily</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.98" spread="4.7"/>
                    <measurement group_id="B2" value="58.78" spread="4.25"/>
                    <measurement group_id="B3" value="57.38" spread="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Patients With Change in HVPG From Baseline</title>
        <description>Number of participants with a decrease in HPVG that was &gt; 10% of baseline</description>
        <time_frame>Three Months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.&#xD;
Placebo: Placebo Comparator: Placebo</description>
          </group>
          <group group_id="O2">
            <title>Sorafenib</title>
            <description>Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.&#xD;
Sorafenib: Sorafenib, 400 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Patients With Change in HVPG From Baseline</title>
          <description>Number of participants with a decrease in HPVG that was &gt; 10% of baseline</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Adverse events were collected at the organ class level, unless specified</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.&#xD;
Placebo: Placebo Comparator: Placebo</description>
        </group>
        <group group_id="E2">
          <title>Sorafenib</title>
          <description>Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.&#xD;
Sorafenib: Sorafenib, 400 mg twice daily</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <description>Patient Hospitalized for Fever</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>gastrointestinal disorders</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General Disorders</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Platelet Count Decrease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Alanine aminostranferase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin Increase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muskoloskeletal and connective tissue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous System Disorders</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric disorders</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Reproductive system and breast disorders</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respitory, thoracic and medistinal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular disorders</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Garcia-Tsao</name_or_title>
      <organization>Yale University</organization>
      <phone>(203) 737-6063</phone>
      <email>guadalupe.garcia-tsao@yale.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01714609
org study id: 1002006266
nct id: NCT01714609
lead sponsor: 
collaborator: 
has dmc: Yes
Sorafenib is approved by the US FDA for the treatment of unresectable (can not operate) liver
      cancer and for renal cell carcinoma. Sorafenib is a drug that inhibits the growth of cancer
      cells and prevents the formation of new blood vessels that would otherwise help the cancer
      spread.

      Studies in experimental animals have shown that sorafenib may also lower portal vein pressure
      (the pressure of the blood passing from the intestine through the liver.) This study seeks to
      determine if sorafenib lowers the blood pressure in liver blood vessels (portal vein
      pressure) in patients with cirrhosis who have high portal vein pressure. The study will also
      obtain information whether sorafenib is safe in this patient population.

      Half of the patients will be given sorafenib and half will be given a placebo (a pill without
      any medicine in it.) This allows a comparison of the reactions of people who take sorafenib
      to those who do not.
This is a pilot proof-of-concept study that investigates the effect of sorafenib on portal
      pressure, as determined by the hepatic venous pressure gradient (HVPG), in patients with
      liver cirrhosis, portal hypertension and unresectable hepatocellular carcinoma (HCC) that has
      successfully responded to radiofrequency ablation and/or transarterial chemoembolization, and
      have obtained a complete response.

      The primary end-point of the study is the change in HVPG observed from baseline to three
      months after starting treatment with sorafenib. Secondary end-point is safety of sorafenib.

      The trial is structured as a randomized double blind placebo controlled study. After a
      three-month period of therapy with sorafenib or placebo (double-blind phase), patients will
      be given open-label sorafenib for an additional 3-month period (open-label phase). A total of
      44 patients will be randomized (in the initial phase) on a 1:1 ratio to sorafenib or placebo.
      Patients will be followed monthly and HCC follow-up will be according to standards of care.
      The study will be sponsored by Onyx, who will also provide the treatment medication
      (sorafenib and placebo)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Patients With Change in HVPG From Baseline
time frame: Three Months
description: Number of participants with a decrease in HPVG that was > 10% of baseline
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
arm group label: Sorafenib
arm group type: Experimental
description: Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
intervention type: Drug
intervention name: Placebo
description: Placebo Comparator: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Sorafenib
description: Sorafenib, 400 mg twice daily
arm group label: Sorafenib
criteria: 
gender: All
minimum age: 20 Years
maximum age: 75 Years
healthy volunteers: No
last name: Guadalupe Garcia-Tsao, MD
role: Principal Investigator
affiliation: Yale University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypertension, Portal
mesh term: Hypertension
mesh term: Sorafenib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 