<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/NCT02241720</url>
  </required_header>
  <id_info>
    <org_study_id>HCI68135</org_study_id>
    <nct_id>NCT02241720</nct_id>
  </id_info>
  <brief_title>Regorafenib Second Line Treatment of Metastatic or Advanced Upper GI Cancers</brief_title>
  <official_title>Regorafenib as a Second Line Single Agent in the Treatment of Metastatic or Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Regorafenib as a Second Line Single Agent in the Treatment of Metastatic or Advanced&#xD;
      Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low Accrual&#xD;
  </why_stopped>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Stable Disease at Eight Weeks Post-Treatment</measure>
    <time_frame>5 months - 3 months treatment and 8 weeks post end of treatment visit</time_frame>
    <description>Patients had disease assessed by CT scans. Stable Disease is defined by any response better than Progression as defined by RECIST 1.1. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Upper GI Cancer</condition>
  <arm_group>
    <arm_group_label>Regorafenib treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>regorafenib</intervention_name>
    <arm_group_label>Regorafenib treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of&#xD;
             the esophagus, gastroesophageal junction or stomach.&#xD;
&#xD;
          -  Patients must show signs of progression during or less than 4 months after being&#xD;
             treated with a first line therapy for their metastatic or locally advanced inoperable&#xD;
             cancer.&#xD;
&#xD;
          -  Patients must have measureable disease at screening by Response Evaluation Criteria&#xD;
             for Solid Tumors 1.1 criteria&#xD;
&#xD;
          -  Age greater than or equal to 18 years.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status 0-1&#xD;
&#xD;
          -  Subjects must be able to understand and be willing to sign the written informed&#xD;
             consent form. A signed informed consent form must be appropriately obtained prior to&#xD;
             the conduct of any trial-specific procedure.&#xD;
&#xD;
          -  All acute toxic effects of any prior treatment have resolved to National Cancer&#xD;
             Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 1 or less&#xD;
             at the time of signing the Informed Consent Form. Alopecia (any grade) and peripheral&#xD;
             neuropathy less than grade 2 is allowed.&#xD;
&#xD;
          -  Adequate bone marrow, liver and liver function as assessed by laboratory requirement&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test performed&#xD;
             within 7 days prior to the start of study drug. Post-menopausal women (defined as no&#xD;
             menses for at least 1 year) and surgically sterilized women are not required to&#xD;
             undergo a pregnancy test.&#xD;
&#xD;
          -  Subjects (men and women) of childbearing potential must agree to use adequate&#xD;
             contraception beginning at the signing of the informed consent form until at least 3&#xD;
             months after the last dose of study drug. Highly effective contraception must be used&#xD;
             (male condom with spermicidal, diaphragm with spermicidal, intra-uterine device) by&#xD;
             both sexes.&#xD;
&#xD;
          -  Subject must be able to swallow and retain oral medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior use of regorafenib&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic pressure greater than 140 mm Hg or diastolic&#xD;
             pressure greater than 90 mm Hg National Cancer Institute Common Terminology Criteria&#xD;
             for Adverse Events version 4.0 on repeated measurement) despite optimal medical&#xD;
             management.&#xD;
&#xD;
          -  Active or clinically significant cardiac disease including:&#xD;
&#xD;
          -  Congestive heart failure - New York Heart Association greater than Class 2.&#xD;
&#xD;
          -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers.&#xD;
&#xD;
          -  Unstable angina (anginal symptoms at rest), new-onset angina within 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 greater than or equal to National Cancer Institute&#xD;
             Common Terminology Criteria for Adverse Events Grade 3 within 4 weeks prior to start&#xD;
             of study medication.&#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 within 6 months of start of study treatment&#xD;
&#xD;
          -  Subjects with any previously untreated or concurrent cancer that is distinct in&#xD;
             primary site or histology except cervical cancer in-situ, treated basal cell&#xD;
             carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was&#xD;
             curatively treated and without evidence of disease for more than 3 years before&#xD;
             randomization are allowed. All cancer treatments must be completed at least 3 years&#xD;
             prior to start of study treatment.&#xD;
&#xD;
          -  Patients with severe hepatic impairment (Child-Pugh Class C)&#xD;
&#xD;
          -  Known history of human immunodeficiency virus infection or current chronic or active&#xD;
             hepatitis B or C infection requiring treatment with antiviral therapy.&#xD;
&#xD;
          -  Patients requiring intravenous antiviral or intravenous antibiotic treatment for&#xD;
             ongoing infections&#xD;
&#xD;
          -  Symptomatic metastatic brain or meningeal tumors.&#xD;
&#xD;
          -  Presence of a non-healing wound, non-healing skin ulcer, or bone fracture.&#xD;
&#xD;
          -  Patient's with a history of kidney disease or persistent proteinuria must have less&#xD;
             than Grade 3 proteinuria per NCI CTCAE v4.0 at screening. If a patient has a history&#xD;
             of kidney disease or persistent proteinuria, a urine protein test will be performed on&#xD;
             a random urine sample. If the result is normal then no additional testing is required.&#xD;
             If the result is abnormal, a 24 hour urine will be collected to determine if&#xD;
             proteinuria is less than Grade 3.&#xD;
&#xD;
          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed&#xD;
             consent.&#xD;
&#xD;
          -  Pleural effusion or ascites that causes respiratory compromise (greater than or equal&#xD;
             to National Cancer Institute Common Terminology Criteria for Adverse Events version&#xD;
             4.0 Grade 2 dyspnea). Patients may undergo thoracentesis and paracentesis to improve&#xD;
             symptoms prior to enrollment.&#xD;
&#xD;
          -  History of organ allograft (including corneal transplant).&#xD;
&#xD;
          -  Known or suspected grade 3 allergy or hypersensitivity to any of the study drugs,&#xD;
             study drug classes, or excipients of the formulations given during the course of this&#xD;
             trial.&#xD;
&#xD;
          -  Any malabsorption condition that in the opinion of the investigator would&#xD;
             significantly impact drug absorption.&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding.&#xD;
&#xD;
          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for&#xD;
             trial participation.&#xD;
&#xD;
          -  Substance abuse, medical, psychological or social conditions that in the opinion of&#xD;
             the investigator may interfere with the subject's participation in the study or&#xD;
             evaluation of the study results.&#xD;
&#xD;
          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,&#xD;
             immunotherapy, biologic therapy, or tumor embolization) within 28 days of starting&#xD;
             study treatment. Palliative radiation is allowed.&#xD;
&#xD;
          -  Concurrent use of another investigational drug or device during, or within 3 weeks of&#xD;
             starting study treatment.&#xD;
&#xD;
          -  Concurrent use of strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine,&#xD;
             phenobarbital, and St. John's Wort)&#xD;
&#xD;
          -  Concurrent use with strong inhibitors of CYP3A4 (e.g. clarithromycin, grapefruit&#xD;
             juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and&#xD;
             voriconazole)&#xD;
&#xD;
          -  Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks&#xD;
             before start of study medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>November 21, 2013</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <results_first_submitted>August 4, 2017</results_first_submitted>
  <results_first_submitted_qc>September 28, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 26, 2017</results_first_posted>
  <last_update_submitted>December 11, 2017</last_update_submitted>
  <last_update_submitted_qc>December 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 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>Gastrointestinal Neoplasms</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Regorafenib Treatment</title>
          <description>160 mg regorafenib by mouth once daily for 3 weeks of every 4 week cycle</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_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Regorafenib Treatment</title>
          <description>regorafenib</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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="5"/>
                  </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="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Stable Disease at Eight Weeks Post-Treatment</title>
        <description>Patients had disease assessed by CT scans. Stable Disease is defined by any response better than Progression as defined by RECIST 1.1. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>5 months - 3 months treatment and 8 weeks post end of treatment visit</time_frame>
        <population>3 subjects did not complete an 8 week EOT visit for: Death, Patient W/D, AE.</population>
        <group_list>
          <group group_id="O1">
            <title>Regorafenib Treatment</title>
            <description>regorafenib</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Stable Disease at Eight Weeks Post-Treatment</title>
          <description>Patients had disease assessed by CT scans. Stable Disease is defined by any response better than Progression as defined by RECIST 1.1. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <population>3 subjects did not complete an 8 week EOT visit for: Death, Patient W/D, AE.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Regorafenib Treatment</title>
          <description>regorafenib</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="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>heart failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Disease Progression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Tracheoesophageal fistula</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" 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"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>hypothyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>dysphagia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>mucositis oral</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </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="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>hyperbilirubinemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>deydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>voice alteration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>aspiration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>maculopapular rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </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>Kimberlee Taylor</name_or_title>
      <organization>Huntsman Cancer Institute</organization>
      <phone>801-213-5673</phone>
      <email>Kimberlee.Taylor@hci.utah.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/NCT02241720
org study id: HCI68135
nct id: NCT02241720
lead sponsor: 
has dmc: Yes
Regorafenib as a Second Line Single Agent in the Treatment of Metastatic or Advanced
      Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Stable Disease at Eight Weeks Post-Treatment
time frame: 5 months - 3 months treatment and 8 weeks post end of treatment visit
description: Patients had disease assessed by CT scans. Stable Disease is defined by any response better than Progression as defined by RECIST 1.1. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
arm group label: Regorafenib treatment
arm group type: Experimental
intervention type: Drug
intervention name: regorafenib
arm group label: Regorafenib treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Gastrointestinal Neoplasms
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 