<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/NCT01719744</url>
  </required_header>
  <id_info>
    <org_study_id>2076-STS-001</org_study_id>
    <nct_id>NCT01719744</nct_id>
  </id_info>
  <brief_title>Study of ENMD-2076 in Patients With Advanced/Metastatic Soft Tissue Sarcoma</brief_title>
  <official_title>A Phase II Study of Oral ENMD-2076 Administered to Patients With Advanced/Metastatic Soft Tissue Sarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2 study of ENMD-2076 in patients with advanced/metastatic soft tissue&#xD;
      sarcoma. This study will help to understand how well ENMD-2076 works and how safe and&#xD;
      tolerable the drug is in this patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ENMD-2076 is an oral drug that works by blocking certain enzymes called Aurora A from&#xD;
      working. These enzymes are needed for cells to divide including cancer cells. ENMD-2076 also&#xD;
      works by stopping the growth of new blood vessels which would provide the tumor with&#xD;
      nutrients for it to grow. It is believed that by blocking Aurora A enzymes from working and&#xD;
      stopping new blood vessels from growing, the tumors may stop growing or shrink.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">December 2015</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>6-month Progression-free Survival Rate (PFS)</measure>
    <time_frame>From start of study treatment until disease progression or death, whichever occurs first, up to 6 months.</time_frame>
    <description>Number of patients with no progression of disease at 6 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of and Severity of Adverse Events Per Participant</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants who experienced a grade 3 or higher adverse event. Reporting threshold 5%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>From start of study treatment until disease progression or death, whichever occurs first.</time_frame>
    <description>Objective Response Rate (ORR) = CR+ PR. ORR is evaluated per RECIST v1.1 criteria.&#xD;
Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Advanced</condition>
  <condition>Metastatic</condition>
  <condition>Soft Tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>ENMD-2076</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ENMD-2076 capsules, 275 mg once daily, by mouth.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ENMD-2076</intervention_name>
    <arm_group_label>ENMD-2076</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have documented histological diagnosis of soft tissue sarcoma (e.g. leiomyosarcoma,&#xD;
             synovial sarcoma, angiosarcoma and liposarcoma etc), with the exception of&#xD;
             gastrointestinal stromal tumor (GIST).&#xD;
&#xD;
          -  Meet revised RECIST criteria (version 1.1) within 4 weeks of entry by having&#xD;
             measurable disease defined as one or more lesions that can be accurately measured in&#xD;
             one or more dimensions. Areas of previous radiation may not serve as measurable&#xD;
             disease unless there has been objective interval tumor growth documented&#xD;
             radiologically.&#xD;
&#xD;
          -  Must have had no more than 1 line of treatment in the advanced/metastatic setting. The&#xD;
             use of prior anti-angiogenic therapy is allowed. Previous neo-adjuvant or adjuvant&#xD;
             therapies are allowed.&#xD;
&#xD;
          -  Are at least 3 weeks from major surgery or radiation therapy and recovered; 3 weeks&#xD;
             from any other previous anticancer therapy and recovered including biologics.&#xD;
&#xD;
          -  Are ≥ 18 years of age&#xD;
&#xD;
          -  The patient has a multigated acquisition (MUGA) scan with an actual left ventricular&#xD;
             ejection fraction of greater than or equal to the institution lower limit of normal&#xD;
             within one month prior to start of study.&#xD;
&#xD;
          -  Have clinically acceptable laboratory screening results within certain limits&#xD;
             specified below:&#xD;
&#xD;
               -  AST and ALT ≤ 2.5 times upper limit of normal (ULN) or less than or equal to 5&#xD;
                  times ULN if liver metastases are present&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5 x ULN or &gt; 50 ml/min calculated by the Cockcroft and Gault&#xD;
                  formula (formula defined in appendix E).&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1500 cells/mm3&#xD;
&#xD;
               -  Platelets ≥ 100,000/mm3&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  INR ≤ 1.5&#xD;
&#xD;
          -  Have an ECOG performance status of 0 or 1.&#xD;
&#xD;
          -  Patients must have and consent for access to archival material (for correlative&#xD;
             studies). Patients who do not have archival material will be eligible if they consent&#xD;
             for fresh tissue biopsy.&#xD;
&#xD;
          -  Women of child producing potential must agree to use effective contraceptive methods&#xD;
             prior to study entry, during study participation, and for at least 30 days after the&#xD;
             last administration of study medication. A serum pregnancy test within 72 hours prior&#xD;
             to the initiation of therapy will be required for women of childbearing potential.&#xD;
&#xD;
          -  Have the ability to understand the requirements of the study, provide written informed&#xD;
             consent which includes authorization for release of protected health information,&#xD;
             abide by the study restrictions, and agree to return for the required assessments.&#xD;
&#xD;
          -  Able to tolerate oral medications.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or nursing&#xD;
&#xD;
          -  Have active, acute, or chronic clinically significant infections or bleeding.&#xD;
&#xD;
          -  Have uncontrolled hypertension (systolic blood pressure greater than 150mmHg or&#xD;
             diastolic blood pressure greater than 100mmHg); or history of congestive heart failure&#xD;
             (equal to or greater than Grade 2 classification by New York Heath Association).&#xD;
&#xD;
          -  Have active angina pectoris, stroke or recent myocardial infarction (within 6 months).&#xD;
&#xD;
          -  Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater&#xD;
             than 480 msec.&#xD;
&#xD;
          -  Have additional uncontrolled serious medical or psychiatric illness.&#xD;
&#xD;
          -  Require therapeutic doses of anti-coagulation either by virtue of low-molecular weight&#xD;
             heparin or coumadin (prophylactic anti-coagulation allowed). Patients with previous&#xD;
             history of deep venous thrombosis or pulmonary embolism are also excluded.&#xD;
&#xD;
          -  Known CNS metastases&#xD;
&#xD;
          -  Have any medical condition that would impair the administration of oral agents&#xD;
             including recurrent bowel obstructions, inflammatory bowel disease or uncontrolled&#xD;
             nausea, vomiting or diarrhea&#xD;
&#xD;
          -  Have 2+ protein by urinalysis. Patients with an ongoing or previous history of&#xD;
             nephrotic syndrome will be excluded&#xD;
&#xD;
          -  Have an additional malignancy diagnosed within 5 years of study enrollment with the&#xD;
             exception of basal or squamous cell skin cancer or cervical cancer in situ&#xD;
&#xD;
          -  Require treatment with drugs known to be potent inducers or inhibitors of CYP3A4 that&#xD;
             cannot be substituted&#xD;
&#xD;
          -  Patients who cannot or refuse to stop herbal medications of illicit drug use will be&#xD;
             excluded from the study. Use of medical marijuana is not permissible in this study.&#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>Albiruni Razak, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Cancer Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>October 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <results_first_submitted>March 28, 2017</results_first_submitted>
  <results_first_submitted_qc>October 30, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">November 7, 2017</results_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ENMD-2076</keyword>
  <keyword>advanced</keyword>
  <keyword>metastatic</keyword>
  <keyword>soft tissue sarcoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>ENMD-2076</title>
          <description>ENMD-2076 capsules, 275 mg once daily, by mouth.&#xD;
ENMD-2076</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>ENMD-2076</title>
          <description>ENMD-2076 capsules, 275 mg once daily, by mouth.&#xD;
ENMD-2076</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </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="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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" lower_limit="22" upper_limit="73"/>
                  </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="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>6-month Progression-free Survival Rate (PFS)</title>
        <description>Number of patients with no progression of disease at 6 months</description>
        <time_frame>From start of study treatment until disease progression or death, whichever occurs first, up to 6 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ENMD-2076</title>
            <description>ENMD-2076 capsules, 275 mg once daily, by mouth.&#xD;
ENMD-2076</description>
          </group>
        </group_list>
        <measure>
          <title>6-month Progression-free Survival Rate (PFS)</title>
          <description>Number of patients with no progression of disease at 6 months</description>
          <units>participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" lower_limit="3" upper_limit="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of and Severity of Adverse Events Per Participant</title>
        <description>Number of participants who experienced a grade 3 or higher adverse event. Reporting threshold 5%</description>
        <time_frame>2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ENMD-2076</title>
            <description>ENMD-2076 capsules, 275 mg once daily, by mouth.&#xD;
ENMD-2076</description>
          </group>
        </group_list>
        <measure>
          <title>Number of and Severity of Adverse Events Per Participant</title>
          <description>Number of participants who experienced a grade 3 or higher adverse event. Reporting threshold 5%</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HYPERTENSION</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DIARRHEA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALANINE AMINOTRANSFERASE INCREASED</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ASPARTATE AMINOTRANSFERASE INCREASED</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VOMITING</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BLOOD BILIRUBIN INCREASED</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HYPOKALEMIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LUNG INFECTION</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HYPOXIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DEHYDRATION</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DEPRESSED LEVEL OF CONSCIOUSNESS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate</title>
        <description>Objective Response Rate (ORR) = CR+ PR. ORR is evaluated per RECIST v1.1 criteria.&#xD;
Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.</description>
        <time_frame>From start of study treatment until disease progression or death, whichever occurs first.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ENMD-2076</title>
            <description>ENMD-2076 capsules, 275 mg once daily, by mouth.&#xD;
ENMD-2076</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate</title>
          <description>Objective Response Rate (ORR) = CR+ PR. ORR is evaluated per RECIST v1.1 criteria.&#xD;
Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="1" upper_limit="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>ENMD-2076</title>
          <description>ENMD-2076 capsules, 275 mg once daily, by mouth.&#xD;
ENMD-2076</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="7" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Reversible posterior leukoencephalopathy syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="25" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANEMIA</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ELECTROCARDIOGRAM QT CORRECTED INTERVAL</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>SINUS TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>SINUS BRADYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTHYROIDISM</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>BLURRED VISION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DIARRHEA</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DYSPEPSIA</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DRY MOUTH</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>MUCOSITIS ORAL</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>FLATULENCE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DYSPHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>TOOTHACHE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ABDOMINAL DISTENSION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>EDEMA LIMBS</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>FEVER</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>FLU LIKE SYMPTOMS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>EDEMA TRUNK</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>LYMPHOCYTE COUNT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>PLATELET COUNT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ALKALINE PHOSPHATASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>WHITE BLOOD CELL DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>CREATININE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>BLOOD BILIRUBIN INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>WEIGHT GAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>NEUTROPHIL COUNT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>WEIGHT LOSS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HEMOGLOBIN INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>GGT INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>LIPASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>HYPOALBUMINEMIA</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>GLUCOSE INTOLERANCE</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPONATREMIA</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPERURICEMIA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPOMAGNESEMIA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ANOREXIA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPERKALEMIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPOGLYCEMIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPOKALEMIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPOCALCEMIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPERGLYCEMIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPOPHOSPHATEMIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>BONE PAIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>MYALGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>GENERALIZED MUSCLE WEAKNESS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DYSGEUSIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>PARESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>CONCENTRATION IMPAIRMENT</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>PROTEINURIA</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HEMATURIA</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>URINARY FREQUENCY</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>DYSPNEA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HOARSENESS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>EPISTAXIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ALOPECIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDRO</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>RASH MACULO-PAPULAR</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>DRY SKIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>HYPERHIDROSIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="25"/>
              </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. ALBIRUNI RAZAK</name_or_title>
      <organization>Princess Margaret Cancer Centre</organization>
      <phone>416-586-4800 ext 5371</phone>
      <email>Albiruni.Razak@uhn.ca</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/NCT01719744
org study id: 2076-STS-001
nct id: NCT01719744
lead sponsor: 
has dmc: Yes
This is a phase 2 study of ENMD-2076 in patients with advanced/metastatic soft tissue
      sarcoma. This study will help to understand how well ENMD-2076 works and how safe and
      tolerable the drug is in this patient population.
ENMD-2076 is an oral drug that works by blocking certain enzymes called Aurora A from
      working. These enzymes are needed for cells to divide including cancer cells. ENMD-2076 also
      works by stopping the growth of new blood vessels which would provide the tumor with
      nutrients for it to grow. It is believed that by blocking Aurora A enzymes from working and
      stopping new blood vessels from growing, the tumors may stop growing or shrink.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 6-month Progression-free Survival Rate (PFS)
time frame: From start of study treatment until disease progression or death, whichever occurs first, up to 6 months.
description: Number of patients with no progression of disease at 6 months
measure: Number of and Severity of Adverse Events Per Participant
time frame: 2 years
description: Number of participants who experienced a grade 3 or higher adverse event. Reporting threshold 5%
measure: Objective Response Rate
time frame: From start of study treatment until disease progression or death, whichever occurs first.
description: Objective Response Rate (ORR) = CR+ PR. ORR is evaluated per RECIST v1.1 criteria.
Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
arm group label: ENMD-2076
arm group type: Experimental
description: ENMD-2076 capsules, 275 mg once daily, by mouth.
intervention type: Drug
intervention name: ENMD-2076
arm group label: ENMD-2076
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Albiruni Razak, MBBS
role: Principal Investigator
affiliation: Princess Margaret Cancer Centre
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Sarcoma
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 