<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/NCT02195232</url>
  </required_header>
  <id_info>
    <org_study_id>14-114</org_study_id>
    <nct_id>NCT02195232</nct_id>
  </id_info>
  <brief_title>Cancer Associated Thrombosis and Isoquercetin (CATIQ)</brief_title>
  <acronym>CATIQ</acronym>
  <official_title>Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jeffrey Zwicker, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quercegen Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is evaluating a drug called isoquercetin to prevent venous thrombosis&#xD;
      (blood clots), in participants who have pancreas, non small cell lung cancer or colorectal&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  This research study is a Phase II/III clinical trial.&#xD;
&#xD;
           --The goal of this trial is to evaluate if isoquercetin can prevent blood clots in&#xD;
           patients with pancreas, non small cell lung cancer or colorectal cancer. In the Phase II&#xD;
           part of this study, the investigators are looking for the dose of isoquercetin to reduce&#xD;
           D-dimer and demonstrate safety.&#xD;
&#xD;
        -  Phase III Endpoint and Treatment Plan&#xD;
&#xD;
             -  Primary Endpoint for Phase III portion of protocol: Cumulative incidence of VTE.&#xD;
&#xD;
             -  Following the completion of the phase II portion, enrolled patients will be&#xD;
                randomized 1:1 to Arm C (isoquercetin) or Arm D (placebo). The dose for Arm C will&#xD;
                be determined after evaluation of the Phase II portion of the trial. The protocol&#xD;
                will be amended when the decision is made whether to proceed to Phase III and what&#xD;
                dose to use for Arm C. The study will be double-blinded to treatment arm. Lower&#xD;
                extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative&#xD;
                labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival&#xD;
                after completion of 56 days.&#xD;
&#xD;
             -  At BIDMC, optional blood draw will be performed at time 0 and 4 hours following the&#xD;
                first dose of study drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Actual">October 22, 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in D-dimer Value</measure>
    <time_frame>Baseline, 56 Day</time_frame>
    <description>D-dimer concentrations will be compared for each patient at day 0 and day 56 by a paired-t test analysis. Analysis will be performed on an intention to treat basis for patients who undergo randomization and completed the baseline and day 56 D-dimer assessments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Hemorrhage</measure>
    <time_frame>study visits until day 56</time_frame>
    <description>Investigating the safety of isoquercetin in cancer patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Incidence of VTE at 56 Days</measure>
    <time_frame>56 days</time_frame>
    <description>To investigate the cumulative incidence of VTE according to tissue factor bearing microparticle status (and isoquercetin randomization).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Thromboembolism of Vein VTE in Colorectal Cancer</condition>
  <condition>Thromboembolism of Vein in Pancreatic Cancer</condition>
  <condition>Thromboembolism of Vein in Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort A - Isoquercetin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>-- Cohort A: 500 mg, Once daily, 28 days&#xD;
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B - Isoquercetin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>--Cohort B: 1000 mg, Once daily, 28 days&#xD;
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoquercetin</intervention_name>
    <arm_group_label>Cohort A - Isoquercetin</arm_group_label>
    <arm_group_label>Cohort B - Isoquercetin</arm_group_label>
    <other_name>quercetin-3-O-glucoside</other_name>
    <other_name>482-35-9</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must meet the following criteria on screening examination to be eligible&#xD;
             to participate in phase 2 and 3 of the study:&#xD;
&#xD;
          -  Participants must have histologically confirmed malignancy that is metastatic or&#xD;
             currently unresectable.&#xD;
&#xD;
          -  Eligible malignancies include:&#xD;
&#xD;
               -  Adenocarcinoma of the pancreas (currently unresectable or metastatic)&#xD;
&#xD;
               -  Colorectal (stage IV)&#xD;
&#xD;
               -  Non-small cell lung cancer (currently unresectable stage III or stage IV)&#xD;
&#xD;
          -  Receiving or scheduled to receive first or second line chemotherapy (within 30 days of&#xD;
             registration)&#xD;
&#xD;
          -  Minimum age 18 years. Because limited dosing or adverse event data are currently&#xD;
             available on the use of isoquercetin in participants &lt;18 years of age, children are&#xD;
             excluded from this study but will be eligible for future pediatric isoquercetin&#xD;
             trials.&#xD;
&#xD;
          -  Life expectancy of greater than 4 months.&#xD;
&#xD;
          -  ECOG performance status ≤2 (see Appendix B ).&#xD;
&#xD;
          -  Patient must be able to swallow capsules (phase III only)&#xD;
&#xD;
          -  Participants must have preserved organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count ≥1,000/mcL&#xD;
&#xD;
               -  Platelets ≥ 90,000/mcL&#xD;
&#xD;
               -  PT and PTT ≤ 1.5 x upper limit of normal&#xD;
&#xD;
               -  Total bilirubin &lt; 2.0 mg/dl&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Creatinine &lt;&#xD;
                  2.0 mg/dl&#xD;
&#xD;
          -  The effects of isoquercetin on the developing human fetus are unknown. For this&#xD;
             reason, women of child-bearing potential and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
             entry and for the duration of study participation. Should a woman become pregnant or&#xD;
             suspect she is pregnant while participating in this study, she should inform her&#xD;
             treating physician immediately.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants may not be receiving any other study agents.&#xD;
&#xD;
          -  Participants with known brain metastases should be excluded from this clinical trial&#xD;
             because of their poor prognosis and because they often develop progressive neurologic&#xD;
             dysfunction that would confound the evaluation of neurologic and other adverse events.&#xD;
&#xD;
          -  Prior history of documented venous thromboembolic event within the last 2 years&#xD;
             (excluding central line associated events whereby patients completed anticoagulation).&#xD;
&#xD;
          -  Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)&#xD;
&#xD;
          -  History of significant hemorrhage (requiring hospitalization or transfusion) outside&#xD;
             of a surgical setting within the last 24 months&#xD;
&#xD;
          -  Familial bleeding diathesis&#xD;
&#xD;
          -  Known diagnosis of disseminated intravascular coagulation (DIC)&#xD;
&#xD;
          -  Currently receiving anticoagulant therapy&#xD;
&#xD;
          -  Current daily use of aspirin (&gt;81mg daily), Clopidogrel (Plavix), cilostazol (Pletal),&#xD;
             aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to use regular use of&#xD;
             higher doses of non-steroidal anti-inflammatory agents as determined by the treating&#xD;
             physician (e.g ibuprofen &gt; 800 mg daily or equivalent).&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Known intolerance of niacin or ascorbic acid (including known G6PD deficiency)&#xD;
&#xD;
          -  Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor&#xD;
             with the potential for teratogenic or abortifacient effects. Because there is an&#xD;
             unknown but potential risk of adverse events in nursing infants secondary to treatment&#xD;
             of the mother with isoquercetin, breastfeeding should be discontinued if the mother is&#xD;
             treated with isoquercetin. These potential risks may also apply to other agents used&#xD;
             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>Jeffrey Zwicker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC/Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Northern California Health Care System</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Connecticut Healthcare System</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06450</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veterans Affair Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>York Hospital-Oncology Treatment Center</name>
      <address>
        <city>York</city>
        <state>Maine</state>
        <zip>03909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston VA Healthcare System</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Auburn Hospital</name>
      <address>
        <city>Waltham</city>
        <state>Massachusetts</state>
        <zip>02138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence VA Medical Center</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>White River Junction VA Medical Center</name>
      <address>
        <city>White River Junction</city>
        <state>Vermont</state>
        <zip>05009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>May 13, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>July 25, 2019</results_first_submitted>
  <results_first_submitted_qc>October 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 12, 2019</results_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Jeffrey Zwicker, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Venous Thromboembolic Events in Cancer Patients</keyword>
  <keyword>Thromboembolism of Vein in Colorectal Cancer</keyword>
  <keyword>Thromboembolism of Vein in Pancreatic Cancer</keyword>
  <keyword>Thromboembolism of Vein in Non-small Cell Lung Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Quercetin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT02195232/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort A (Isoquercetin 500 mg)</title>
          <description>Patients will receive isoquercetin 500 mg once daily (2 capsules).</description>
        </group>
        <group group_id="P2">
          <title>Cohort B (Isoquercetin 1000 mg)</title>
          <description>Patients will receive isoquercetin 1000 mg once daily (4 capsules).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32">patients consented</participants>
                <participants group_id="P2" count="32">patients consented</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28">Evaluated for VTE and safety</participants>
                <participants group_id="P2" count="29">Evaluated for VTE and safety</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort A (Isoquercetin 500 mg)</title>
          <description>Patients will receive isoquercetin 500 mg once daily (2 capsules).</description>
        </group>
        <group group_id="B2">
          <title>Cohort B (Isoquercetin 1000 mg)</title>
          <description>Patients will receive isoquercetin 1000 mg once daily (4 capsules).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
            <count group_id="B2" value="32"/>
            <count group_id="B3" value="64"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Evaluated for VTE and safety</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="28"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="57"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Evaluated for VTE and safety</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="28"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="57"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Evaluated for VTE and safety</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="28"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="57"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <population>Evaluated for VTE and safety</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="28"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="57"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in D-dimer Value</title>
        <description>D-dimer concentrations will be compared for each patient at day 0 and day 56 by a paired-t test analysis. Analysis will be performed on an intention to treat basis for patients who undergo randomization and completed the baseline and day 56 D-dimer assessments.</description>
        <time_frame>Baseline, 56 Day</time_frame>
        <population>The analysis data set is comprised of evaluable patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A (Isoquercetin 500 mg)</title>
            <description>Patients will receive isoquercetin 500 mg once daily (2 capsules).</description>
          </group>
          <group group_id="O2">
            <title>Cohort B (Isoquercetin 1000 mg)</title>
            <description>Patients will receive isoquercetin 1000 mg once daily (4 capsules).</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in D-dimer Value</title>
          <description>D-dimer concentrations will be compared for each patient at day 0 and day 56 by a paired-t test analysis. Analysis will be performed on an intention to treat basis for patients who undergo randomization and completed the baseline and day 56 D-dimer assessments.</description>
          <population>The analysis data set is comprised of evaluable patients.</population>
          <units>percent change</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9" lower_limit="-51.1" upper_limit="74.2"/>
                    <measurement group_id="O2" value="-21.9" lower_limit="-63.3" upper_limit="36.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.92</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Hemorrhage</title>
        <description>Investigating the safety of isoquercetin in cancer patients</description>
        <time_frame>study visits until day 56</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort A (Isoquercetin 500 mg)</title>
            <description>Cohort A: Patients will receive isoquercetin 500 mg once daily (2 capsules) for 28 days.&#xD;
Lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.</description>
          </group>
          <group group_id="O2">
            <title>Cohort B (Isoquercetin 1000 mg)</title>
            <description>Cohort B: Patients will receive isoquercetin 1000 mg once daily (4 capsules) for 28 days.&#xD;
Lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Hemorrhage</title>
          <description>Investigating the safety of isoquercetin in cancer patients</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Incidence of VTE at 56 Days</title>
        <description>To investigate the cumulative incidence of VTE according to tissue factor bearing microparticle status (and isoquercetin randomization).</description>
        <time_frame>56 days</time_frame>
        <population>All patients who began assigned treatment were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A - Isoquercetin</title>
            <description>-- Cohort A: 500 mg, Once daily, 28 days&#xD;
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.&#xD;
Isoquercetin</description>
          </group>
          <group group_id="O2">
            <title>Cohort B - Isoquercetin</title>
            <description>--Cohort B: 1000 mg, Once daily, 28 days&#xD;
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.&#xD;
Isoquercetin</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Incidence of VTE at 56 Days</title>
          <description>To investigate the cumulative incidence of VTE according to tissue factor bearing microparticle status (and isoquercetin randomization).</description>
          <population>All patients who began assigned treatment were analyzed.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events data were collected form the time of the first dose (Day 1) of study treatment, through the study and until the final study visit (Day 56).</time_frame>
      <desc>All serious adverse events that occur after the initial dose of study treatment, during treatment, or within 30 days of the last dose of treatment must be reported to the Overall Principal Investigator.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort A (Isoquercetin 500 mg)</title>
          <description>Cohort A: Patients will receive isoquercetin 500 mg once daily (2 capsules) for 28 days.&#xD;
Lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.</description>
        </group>
        <group group_id="E2">
          <title>Cohort B (Isoquercetin 1000 mg)</title>
          <description>Cohort B: Patients will receive isoquercetin 1000 mg once daily (4 capsules) for 28 days.&#xD;
Lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.</description>
        </group>
      </group_list>
      <serious_events>
        <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="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE) version 4.03</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="11" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastrointestinal</sub_title>
                <description>Lower gastrointestinal hemorrhage</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </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>Jeffrey Zwicker, Division of Thrombosis and Haemostasis, Division of Hematology and Oncology</name_or_title>
      <organization>Beth Israel Deaconess Medical Center, Harvard Medical School</organization>
      <phone>617.667.9299</phone>
      <email>jzwicker@bidmc.harvard.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/NCT02195232
org study id: 14-114
nct id: NCT02195232
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This research study is evaluating a drug called isoquercetin to prevent venous thrombosis
      (blood clots), in participants who have pancreas, non small cell lung cancer or colorectal
      cancer.
-  This research study is a Phase II/III clinical trial.

           --The goal of this trial is to evaluate if isoquercetin can prevent blood clots in
           patients with pancreas, non small cell lung cancer or colorectal cancer. In the Phase II
           part of this study, the investigators are looking for the dose of isoquercetin to reduce
           D-dimer and demonstrate safety.

        -  Phase III Endpoint and Treatment Plan

             -  Primary Endpoint for Phase III portion of protocol: Cumulative incidence of VTE.

             -  Following the completion of the phase II portion, enrolled patients will be
                randomized 1:1 to Arm C (isoquercetin) or Arm D (placebo). The dose for Arm C will
                be determined after evaluation of the Phase II portion of the trial. The protocol
                will be amended when the decision is made whether to proceed to Phase III and what
                dose to use for Arm C. The study will be double-blinded to treatment arm. Lower
                extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative
                labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival
                after completion of 56 days.

             -  At BIDMC, optional blood draw will be performed at time 0 and 4 hours following the
                first dose of study drug.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Change in D-dimer Value
time frame: Baseline, 56 Day
description: D-dimer concentrations will be compared for each patient at day 0 and day 56 by a paired-t test analysis. Analysis will be performed on an intention to treat basis for patients who undergo randomization and completed the baseline and day 56 D-dimer assessments.
measure: Number of Participants With Hemorrhage
time frame: study visits until day 56
description: Investigating the safety of isoquercetin in cancer patients
measure: Cumulative Incidence of VTE at 56 Days
time frame: 56 days
description: To investigate the cumulative incidence of VTE according to tissue factor bearing microparticle status (and isoquercetin randomization).
arm group label: Cohort A - Isoquercetin
arm group type: Experimental
description: -- Cohort A: 500 mg, Once daily, 28 days
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.
arm group label: Cohort B - Isoquercetin
arm group type: Experimental
description: --Cohort B: 1000 mg, Once daily, 28 days
- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.
intervention type: Drug
intervention name: Isoquercetin
arm group label: Cohort A - Isoquercetin
arm group label: Cohort B - Isoquercetin
other name: quercetin-3-O-glucoside
other name: 482-35-9
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey Zwicker, MD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Jeffrey Zwicker, MD
investigator title: Principal Investigator
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Colorectal Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Thromboembolism
mesh term: Quercetin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 