<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/NCT02234180</url>
  </required_header>
  <id_info>
    <org_study_id>RU021212I</org_study_id>
    <secondary_id>NCI-2015-01699</secondary_id>
    <secondary_id>NCI-2014-01962</secondary_id>
    <secondary_id>RU021212I</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT02234180</nct_id>
  </id_info>
  <brief_title>Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery</brief_title>
  <official_title>Randomized Phase II Double Blind Study of Adjuvant Regorafenib vs Placebo in Patients With Node Positive Esophageal Cancer That Completed Pre-operative Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Academic and Community Cancer Research United</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Academic and Community Cancer Research United</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well regorafenib works in treating patients with&#xD;
      cancer of the esophagus or gastroesophageal junction that has spread from where it started to&#xD;
      nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery.&#xD;
      Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for&#xD;
      cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the disease-free survival (DFS) for patients with resected esophageal and&#xD;
      gastroesophageal (GE) junction adenocarcinoma treated with regorafenib vs. placebo in the&#xD;
      adjuvant setting.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the safety profile of adjuvant regorafenib vs. placebo in patients with locally&#xD;
      advanced resectable esophageal and GE junction adenocarcinoma.&#xD;
&#xD;
      II. To compare the overall survival (OS) for patients with resected esophageal and GE&#xD;
      junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.&#xD;
&#xD;
      III. To compare the DFS in those patients that receive at least 1 cycle of therapy.&#xD;
&#xD;
      IV. To collect tumor samples for future genomic analysis to explore the biology of locally&#xD;
      advanced esophageal and GE junction adenocarcinoma.&#xD;
&#xD;
      V. DFS will be compared between the arms from the time of surgery as well.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Within 6-12 weeks after surgery, patients receive regorafenib orally (PO) once daily&#xD;
      (QD) on days 1-21.&#xD;
&#xD;
      ARM II: Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21.&#xD;
&#xD;
      In both arms, courses repeat every 28 days for up to 1 year in the absence of disease&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 2 years, and&#xD;
      every 6 months for up to 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">June 8, 2016</completion_date>
  <primary_completion_date type="Actual">June 8, 2016</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>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Free Survival (DFS)</measure>
    <time_frame>Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months</time_frame>
    <description>Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</measure>
    <time_frame>Up to 1 year and 10 months</time_frame>
    <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Time from randomization to death due to any cause, assessed up to 1 year and 10 months</time_frame>
    <description>Overall survival (OS) is defined as the time from randomization to death due to any cause.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Adenocarcinoma of the Gastroesophageal Junction</condition>
  <condition>Stage IIB Esophageal Adenocarcinoma</condition>
  <condition>Stage IIIA Esophageal Adenocarcinoma</condition>
  <condition>Stage IIIB Esophageal Adenocarcinoma</condition>
  <condition>Stage IIIC Esophageal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (regorafenib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Within 6-12 weeks after surgery, patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <other_name>placebo therapy</other_name>
    <other_name>PLCB</other_name>
    <other_name>sham therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regorafenib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (regorafenib)</arm_group_label>
    <other_name>BAY 73-4506</other_name>
    <other_name>Stivarga</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological confirmation of node positive (any T stage N1-3) proximal esophageal,&#xD;
             distal esophagus or gastroesophageal (GE) junction adenocarcinoma (Siewert I, II, or&#xD;
             III) after completing preoperative chemoradiation and surgery; supporting pathology&#xD;
             report sufficient for registration; available tumor tissue from endoscopic biopsies&#xD;
             prior to preoperative chemotherapy (chemo)/radiation therapy (RT), and tumor from&#xD;
             surgical specimens will be submitted to Academic and Community Cancer Research United&#xD;
             (ACCRU), but not be required prior registration; Note: if tissue is depleted, patient&#xD;
             will still be eligible after discussion with the physician&#xD;
&#xD;
          -  Imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) =&lt; 28 days of&#xD;
             study registration negative for disease recurrence&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x the upper limits of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN (=&lt; 5&#xD;
             x ULN for subjects with liver involvement of their cancer)&#xD;
&#xD;
          -  Alkaline phosphatase limit =&lt; 2.5 x ULN (=&lt; 5 x ULN for subjects with liver&#xD;
             involvement of their cancer)&#xD;
&#xD;
          -  Lipase =&lt; 1.5 x the ULN&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x the ULN&#xD;
&#xD;
          -  International normalized ratio (INR)/partial thromboplastin time (PTT) =&lt; 1.5 x ULN;&#xD;
             Note-subjects who are therapeutically treated with an agent such as warfarin or&#xD;
             heparin will be allowed to participate provided that their medication dose and INR/PTT&#xD;
             are stable; close monitoring (day 1 of each cycle) is mandatory; if either of these&#xD;
             values is above the therapeutic range, the doses should be modified and the&#xD;
             assessments should be repeated weekly until they are stable&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Provide informed written consent&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring&#xD;
             Phase of the study)&#xD;
&#xD;
          -  Able to swallow and retain oral medications and begin therapy within 6 to 12 weeks&#xD;
             post-surgery&#xD;
&#xD;
          -  Provide blood samples for the mandatory correlative research purposes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of metastatic or recurrent disease&#xD;
&#xD;
          -  R1 or R2 resection&#xD;
&#xD;
          -  Patients who have not recovered from serious adverse events (as determined by treating&#xD;
             doctor of medicine [MD]) related to surgery&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic pressure &gt; 140 mm Hg or diastolic pressure &gt; 90 mm&#xD;
             Hg on repeated measurement) despite optimal medical management per physician&#xD;
             discretion&#xD;
&#xD;
          -  Active or clinically significant cardiac disease including:&#xD;
&#xD;
               -  Congestive heart failure - New York Heart Association (NYHA) &gt; class II&#xD;
&#xD;
               -  Active coronary artery disease&#xD;
&#xD;
               -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or&#xD;
                  digoxin&#xD;
&#xD;
               -  Unstable angina (anginal symptoms at rest), new-onset angina &lt; 3 months before&#xD;
                  randomization, or myocardial infarction within 6 months before randomization&#xD;
&#xD;
          -  Evidence or history of bleeding diathesis or coagulopathy&#xD;
&#xD;
          -  Any hemorrhage or bleeding event &gt;= National Cancer Institute Common Terminology&#xD;
             Criteria for Adverse Events (NCI CTCAE) version 4 grade 3 =&lt; 4 weeks prior to&#xD;
             registration&#xD;
&#xD;
          -  Prior cancers &lt; 3 years, with the exception of in-situ cervical cancer, low grade&#xD;
             prostate cancer and basal or squamous cell skin cancers&#xD;
&#xD;
          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular&#xD;
             accident (including transient ischemic attacks) deep vein thrombosis or pulmonary&#xD;
             embolism =&lt; 6 months prior to registration&#xD;
&#xD;
          -  Receiving any medications or substances that are strong or moderate inhibitors of&#xD;
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of strong or&#xD;
             moderate inhibitors are prohibited =&lt; 7 days to registration&#xD;
&#xD;
          -  Receiving any medications or substances that are inducers of CYP3A4; use of inducers&#xD;
             are prohibited =&lt; 7 days prior to registration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yelena Janjigian</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academic and Community Cancer Research United</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carle Cancer Center</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Wichita</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center Jefferson</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</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>Missouri Valley Cancer Consortium</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Center of Wake Forest University</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toledo Clinic Cancer Centers-Toledo</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <results_first_submitted>August 13, 2018</results_first_submitted>
  <results_first_submitted_qc>October 15, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 17, 2018</results_first_posted>
  <last_update_submitted>October 15, 2018</last_update_submitted>
  <last_update_submitted_qc>October 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Regorafenib)</title>
          <description>Within 6-12 weeks after surgery, patients will receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Placebo)</title>
          <description>Within 6-12 weeks after surgery, patients will receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated.</population>
      <group_list>
        <group group_id="B1">
          <title>Arm I/II (Regorafenib/Placebo)</title>
          <description>Within 6-12 weeks after surgery, patients receive regorafenib OR placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.0" lower_limit="53.0" upper_limit="58.0"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Disease Free Survival (DFS)</title>
        <description>Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.</description>
        <time_frame>Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months</time_frame>
        <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I/II (Regorafenib/Placebo)</title>
            <description>Within 6-12 weeks after surgery, patients receive regorafenib OR placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Free Survival (DFS)</title>
          <description>Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.</description>
          <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.83" lower_limit="2.27" upper_limit="9.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</title>
        <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
        <time_frame>Up to 1 year and 10 months</time_frame>
        <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I/II (Regorafenib/Placebo)</title>
            <description>Within 6-12 weeks after surgery, patients receive regorafenib OR placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</title>
          <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
          <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.</population>
          <units>percentage of grade 3+ AEs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall survival (OS) is defined as the time from randomization to death due to any cause.</description>
        <time_frame>Time from randomization to death due to any cause, assessed up to 1 year and 10 months</time_frame>
        <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I/II (Regorafenib/Placebo)</title>
            <description>Within 6-12 weeks after surgery, patients receive regorafenib OR placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall survival (OS) is defined as the time from randomization to death due to any cause.</description>
          <population>Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">No OS events observed among the patients, thus no OS median and 95% confidence interval is available.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 1 year and 10 months</time_frame>
      <desc>The descriptions &amp; grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation &amp; scientific analysis &amp; is a single MedDRA Lowest Level Term (LLT). Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm I/II (Regorafenib/Placebo)</title>
          <description>Within 6-12 weeks after surgery, patients receive regorafenib OR placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 12</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 12</default_vocab>
        <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="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Yelena Y. Janjigian MD</name_or_title>
      <organization>Memorial Sloan-Kettering Cancer Center</organization>
      <phone>646-888-4186</phone>
      <email>janjigiy@mskcc.org</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/NCT02234180
org study id: RU021212I
secondary id: NCI-2015-01699
secondary id: NCI-2014-01962
secondary id: RU021212I
secondary id: P30CA015083
nct id: NCT02234180
lead sponsor: 
collaborator: 
has dmc: Yes
This randomized phase II trial studies how well regorafenib works in treating patients with
      cancer of the esophagus or gastroesophageal junction that has spread from where it started to
      nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery.
      Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth.
PRIMARY OBJECTIVES:

      I. To compare the disease-free survival (DFS) for patients with resected esophageal and
      gastroesophageal (GE) junction adenocarcinoma treated with regorafenib vs. placebo in the
      adjuvant setting.

      SECONDARY OBJECTIVES:

      I. To compare the safety profile of adjuvant regorafenib vs. placebo in patients with locally
      advanced resectable esophageal and GE junction adenocarcinoma.

      II. To compare the overall survival (OS) for patients with resected esophageal and GE
      junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.

      III. To compare the DFS in those patients that receive at least 1 cycle of therapy.

      IV. To collect tumor samples for future genomic analysis to explore the biology of locally
      advanced esophageal and GE junction adenocarcinoma.

      V. DFS will be compared between the arms from the time of surgery as well.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Within 6-12 weeks after surgery, patients receive regorafenib orally (PO) once daily
      (QD) on days 1-21.

      ARM II: Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21.

      In both arms, courses repeat every 28 days for up to 1 year in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years, and
      every 6 months for up to 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Disease Free Survival (DFS)
time frame: Time from randomization to the first of either disease recurrence or death from any cause, assessed up to 1 year and 10 months
description: Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.
measure: Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
time frame: Up to 1 year and 10 months
description: The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
measure: Overall Survival (OS)
time frame: Time from randomization to death due to any cause, assessed up to 1 year and 10 months
description: Overall survival (OS) is defined as the time from randomization to death due to any cause.
arm group label: Arm I (regorafenib)
arm group type: Experimental
description: Within 6-12 weeks after surgery, patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (placebo)
arm group type: Placebo Comparator
description: Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Placebo
description: Given PO
arm group label: Arm II (placebo)
other name: placebo therapy
other name: PLCB
other name: sham therapy
intervention type: Drug
intervention name: Regorafenib
description: Given PO
arm group label: Arm I (regorafenib)
other name: BAY 73-4506
other name: Stivarga
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yelena Janjigian
role: Principal Investigator
affiliation: Academic and Community Cancer Research United
facility: 
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Esophageal Neoplasms
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 