<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/NCT01722162</url>
  </required_header>
  <id_info>
    <org_study_id>201303043</org_study_id>
    <nct_id>NCT01722162</nct_id>
  </id_info>
  <brief_title>Levocetirizine + Capecitabine + Bevacizumab for Patients With Refractory Colorectal Cancer</brief_title>
  <official_title>Phase II Study of Levocetirizine in Combination With Capecitabine + Bevacizumab to Overcome Resistance to Anti-angiogenic Therapy in Patients With Refractory Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how giving a drug called levocetirizine to patients&#xD;
      with colorectal cancer affects their tumor response to capecitabine and bevacizumab.&#xD;
      Capecitabine is a chemotherapy drug that blocks tumor growth by disrupting DNA and RNA&#xD;
      synthesis and repair (cell division and survival). Bevacizumab is a monoclonal antibody that&#xD;
      blocks the ability of tumors to grow and spread by inhibiting the growth of blood vessels&#xD;
      that feed them. Patients with colorectal cancer can develop a resistance to the effects of&#xD;
      bevacizumab. Levocetirizine may decrease tumor resistance to bevacizumab. Giving bevacizumab,&#xD;
      capecitabine, and levocetirizine dihydrochloride together may be an effective treatment for&#xD;
      refractory colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2013</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (Arm A)</measure>
    <time_frame>Until progressive disease (PD) (estimated to be 92 days)</time_frame>
    <description>Time from start of treatment to the time of progression or death, whichever occurs first&#xD;
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.&#xD;
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (Arm B)</measure>
    <time_frame>Until progressive disease (PD) (up to 60 days)</time_frame>
    <description>Time from start of treatment to the time of progression or death, whichever occurs first&#xD;
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.&#xD;
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of Adverse Events as Measured by Number of Participants Who Experience Grade 3 and Higher Adverse Events</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Colorectal Neoplasms</condition>
  <arm_group>
    <arm_group_label>Arm A: (start levocetirizine after bevacizumab/capecitabine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: (start levocetirizine before bevacizumab/capecitabine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <arm_group_label>Arm A: (start levocetirizine after bevacizumab/capecitabine)</arm_group_label>
    <arm_group_label>Arm B: (start levocetirizine before bevacizumab/capecitabine)</arm_group_label>
    <other_name>Avastin®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <arm_group_label>Arm A: (start levocetirizine after bevacizumab/capecitabine)</arm_group_label>
    <arm_group_label>Arm B: (start levocetirizine before bevacizumab/capecitabine)</arm_group_label>
    <other_name>Xeloda®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levocetirizine</intervention_name>
    <arm_group_label>Arm A: (start levocetirizine after bevacizumab/capecitabine)</arm_group_label>
    <arm_group_label>Arm B: (start levocetirizine before bevacizumab/capecitabine)</arm_group_label>
    <other_name>Xyzal</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must have histologically or cytologically confirmed refractory colorectal&#xD;
             cancer (CRC).&#xD;
&#xD;
          -  Patient must have measurable disease defined as lesions that can be accurately&#xD;
             measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT&#xD;
             scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam.&#xD;
&#xD;
          -  Patient must have documented progressive disease within 3 months of his/her most&#xD;
             recent cycle of chemotherapy.&#xD;
&#xD;
          -  Patient must be refractory to or intolerant of prior therapy with a fluoropyrimidine,&#xD;
             oxaliplatin, irinotecan, and/or anti-angiogenic therapy. Patients with K-RAS wild type&#xD;
             tumors must have received an epidermal growth factor receptor (EGFR) inhibitor such as&#xD;
             cetuximab or panitumumab.&#xD;
&#xD;
          -  Patient must be ≥ 18 years of age.&#xD;
&#xD;
          -  Patient must have an ECOG performance status ≤ 2&#xD;
&#xD;
          -  Patient must have normal bone marrow and organ function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,500/mcl&#xD;
&#xD;
               -  Platelets ≥ 100,000/mcl&#xD;
&#xD;
               -  Total bilirubin ≤ 2.0 x IULN&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN&#xD;
&#xD;
               -  Patients must have adequate renal function prior to chemotherapy defined as serum&#xD;
                  creatinine ≤ 2.0 mg/dl OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients&#xD;
                  with creatinine levels above 2.0&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while participating in this study, she must inform her treating physician&#xD;
             immediately.&#xD;
&#xD;
          -  Patient must be able to understand and willing to sign an IRB approved written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient must not have a history of other malignancy ≤ 3 years previous with the&#xD;
             exception of basal cell or squamous cell carcinoma of the skin which were treated with&#xD;
             local resection only or carcinoma in situ of the cervix.&#xD;
&#xD;
          -  Patient must not be receiving any other investigational agents.&#xD;
&#xD;
          -  Patient must not have known active brain metastases. Patients with previously treated&#xD;
             brain metastases are eligible. Patients with known brain active metastases must be&#xD;
             excluded from this clinical trial because of their poor prognosis and because they&#xD;
             often develop progressive neurologic dysfunction that would confound the evaluation of&#xD;
             neurologic and other adverse events.&#xD;
&#xD;
          -  Patient must not have a history of allergic reactions attributed to compounds of&#xD;
             similar chemical or biologic composition to levocetirizine, capecitabine, bevacizumab,&#xD;
             or other agents used in the study.&#xD;
&#xD;
          -  Patient must not have known dihydropyrimidine dehydrogenase (DPD) deficiency or severe&#xD;
             renal impairment (creatinine clearance below 30 mL/min by Cockcroft and Gault formula)&#xD;
             as this would prelude use of capecitabine.&#xD;
&#xD;
          -  Patient must not have known proteinuria ≥ 500mg/24 hours.&#xD;
&#xD;
          -  Patient must not have an uncontrolled intercurrent illness including, but not limited&#xD;
             to, ongoing or active infection, symptomatic congestive heart failure, unstable angina&#xD;
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would&#xD;
             limit compliance with study requirements.&#xD;
&#xD;
          -  Patient must not be pregnant and/or breastfeeding. Patient must have a negative urine&#xD;
             pregnancy test within seven days of study entry.&#xD;
&#xD;
          -  Patient must not be known to be HIV-positive on combination antiretroviral because of&#xD;
             the potential for pharmacokinetic interactions with levocetirizine, capecitabine, and&#xD;
             bevacizumab. In addition, these patients are at increased risk of lethal infections&#xD;
             when treated with marrow-suppressive therapy. Appropriate studies will be undertaken&#xD;
             in patients receiving combination antiretroviral therapy when indicated.&#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>Manik A Amin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <results_first_submitted>December 20, 2016</results_first_submitted>
  <results_first_submitted_qc>December 20, 2016</results_first_submitted_qc>
  <results_first_posted type="Actual">February 13, 2017</results_first_posted>
  <last_update_submitted>March 22, 2017</last_update_submitted>
  <last_update_submitted_qc>March 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Levocetirizine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study opened to patient enrollment on 04/26/2013 and closed to patient enrollment on 07/15/2015.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm A: (Start Levocetirizine After Bevacizumab/Capecitabine)</title>
          <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
        </group>
        <group group_id="P2">
          <title>Arm B: (Start Levocetirizine Before Bevacizumab/Capecitabine)</title>
          <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Found ineligible</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unrelated to study adverse event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Insurance denial post enrollment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Noncompliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm A: (Start Levocetirizine After Bevacizumab/Capecitabine)</title>
          <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
        </group>
        <group group_id="B2">
          <title>Arm B: (Start Levocetirizine Before Bevacizumab/Capecitabine)</title>
          <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.</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="23"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="39" upper_limit="80"/>
                    <measurement group_id="B2" value="57.5" lower_limit="36" upper_limit="76"/>
                    <measurement group_id="B3" value="60" lower_limit="36" upper_limit="80"/>
                  </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="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (Arm A)</title>
        <description>Time from start of treatment to the time of progression or death, whichever occurs first&#xD;
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.&#xD;
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.</description>
        <time_frame>Until progressive disease (PD) (estimated to be 92 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: (Start Levocetirizine After Bevacizumab/Capecitabine)</title>
            <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (Arm A)</title>
          <description>Time from start of treatment to the time of progression or death, whichever occurs first&#xD;
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.&#xD;
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.</description>
          <units>proportion of patients with PFS</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PFS Days = 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.946" lower_limit="0.848" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.892" lower_limit="0.761" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 43</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.739" lower_limit="0.567" upper_limit="0.964"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 46</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.685" lower_limit="0.505" upper_limit="0.929"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.630" lower_limit="0.446" upper_limit="0.890"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 92</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.575" lower_limit="0.390" upper_limit="0.849"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence and Severity of Adverse Events as Measured by Number of Participants Who Experience Grade 3 and Higher Adverse Events</title>
        <description>NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</description>
        <time_frame>Up to 6 months</time_frame>
        <population>Arm A: 4 patients not evaluable for outcome measure (2 had unrelated adverse events after enrollment but prior to treatment, 1 withdrew consent after enrollment but prior to treatment, &amp; 1 was found ineligible after enrollment but prior to treatment). Arm B: 1 patient not evaluable because of noncompliance after enrollment but before treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: (Start Levocetirizine After Bevacizumab/Capecitabine)</title>
            <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
          </group>
          <group group_id="O2">
            <title>Arm B: (Start Levocetirizine Before Bevacizumab/Capecitabine)</title>
            <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence and Severity of Adverse Events as Measured by Number of Participants Who Experience Grade 3 and Higher Adverse Events</title>
          <description>NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</description>
          <population>Arm A: 4 patients not evaluable for outcome measure (2 had unrelated adverse events after enrollment but prior to treatment, 1 withdrew consent after enrollment but prior to treatment, &amp; 1 was found ineligible after enrollment but prior to treatment). Arm B: 1 patient not evaluable because of noncompliance after enrollment but before treatment</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Small intestinal obstruction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood bilirubin increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Peripheral motor neuropathy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Peripheral sensory neuropathy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thromboembolic event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart failure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Colonic fistula</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Colonic perforation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gram-negative bacilli infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clostridium bloodstream infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anorexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bone pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Generalized muscle weakness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Muscle weakness lower limbs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urinary retention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory failure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (Arm B)</title>
        <description>Time from start of treatment to the time of progression or death, whichever occurs first&#xD;
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.&#xD;
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.</description>
        <time_frame>Until progressive disease (PD) (up to 60 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: (Start Levocetirizine After Bevacizumab/Capecitabine)</title>
            <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (Arm B)</title>
          <description>Time from start of treatment to the time of progression or death, whichever occurs first&#xD;
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.&#xD;
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.</description>
          <units>proportion of patients with PFS</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PFS Days = 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.946" lower_limit="0.848" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 33</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.892" lower_limit="0.761" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 44</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.838" lower_limit="0.686" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.686" lower_limit="0.507" upper_limit="0.928"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.631" lower_limit="0.448" upper_limit="0.890"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS Days = 60</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.576" lower_limit="0.391" upper_limit="0.849"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Arm A: 4 patients not evaluable for serious adverse event and adverse event collection (2 had unrelated adverse events after enrollment but prior to treatment, 1 withdrew consent after enrollment but prior to treatment, &amp; 1 was found ineligible after enrollment but prior to treatment). Arm B: 1 patient not evaluable for serious adverse event and adverse event collection because of noncompliance after enrollment but before treatment</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm A: (Start Levocetirizine After Bevacizumab/Capecitabine)</title>
          <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.</description>
        </group>
        <group group_id="E2">
          <title>Arm B: (Start Levocetirizine Before Bevacizumab/Capecitabine)</title>
          <description>Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.&#xD;
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.&#xD;
Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="23"/>
              </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="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Colonic fistula</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Illeal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Small bowel obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death due to disease progression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Generalized weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </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="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="19" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="23"/>
              </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="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal cramps</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Bleeding at stroma site</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Colonic perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hemmorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Edema - limbs</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Sweating</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Clostridium bloodstream infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Food poisoning &quot;stomach flu&quot;</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Gram-negative bacilli infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Right groin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Shingles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Buttock pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Cramping in hands and feet</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Foot pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Muscle cramps</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limbs</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry nasal passages</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Sinus disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Trachypneic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Brittle nails</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Facial rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Palmar-Planter erythrodysethsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Skin pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Sores on head</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Cataract surgery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </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>Manik A. Amin, M.D.</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-362-9115</phone>
      <email>manikamin@wustl.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/NCT01722162
org study id: 201303043
nct id: NCT01722162
lead sponsor: 
has dmc: No
This randomized phase II trial studies how giving a drug called levocetirizine to patients
      with colorectal cancer affects their tumor response to capecitabine and bevacizumab.
      Capecitabine is a chemotherapy drug that blocks tumor growth by disrupting DNA and RNA
      synthesis and repair (cell division and survival). Bevacizumab is a monoclonal antibody that
      blocks the ability of tumors to grow and spread by inhibiting the growth of blood vessels
      that feed them. Patients with colorectal cancer can develop a resistance to the effects of
      bevacizumab. Levocetirizine may decrease tumor resistance to bevacizumab. Giving bevacizumab,
      capecitabine, and levocetirizine dihydrochloride together may be an effective treatment for
      refractory colorectal cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival (Arm A)
time frame: Until progressive disease (PD) (estimated to be 92 days)
description: Time from start of treatment to the time of progression or death, whichever occurs first
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
measure: Progression Free Survival (Arm B)
time frame: Until progressive disease (PD) (up to 60 days)
description: Time from start of treatment to the time of progression or death, whichever occurs first
Progressive disease (target lesions): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Progressive disease (non-target lesions): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
measure: Incidence and Severity of Adverse Events as Measured by Number of Participants Who Experience Grade 3 and Higher Adverse Events
time frame: Up to 6 months
description: NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
arm group label: Arm A: (start levocetirizine after bevacizumab/capecitabine)
arm group type: Experimental
description: Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.
Levocetirizine PO 5 mg daily before bed starting on Day 8 of Cycle 1. 5 mg daily before bed Days 1-4 of each cycle starting with cycle 2.
arm group label: Arm B: (start levocetirizine before bevacizumab/capecitabine)
arm group type: Experimental
description: Bevacizumab IV 5 mg/kg on Days 1 each 2-week cycle.
Capecitabine PO 850 mg/m2 twice a day on Days 1-7 of each 2 week cycle.
Levocetirizine PO 5 mg daily starting 7 days prior to initiation of bevacizumab and capecitabine therapy. 5 mg daily Days 1-14 starting with cycle 2.
intervention type: Drug
intervention name: Bevacizumab
arm group label: Arm A: (start levocetirizine after bevacizumab/capecitabine)
arm group label: Arm B: (start levocetirizine before bevacizumab/capecitabine)
other name: Avastin®
intervention type: Drug
intervention name: Capecitabine
arm group label: Arm A: (start levocetirizine after bevacizumab/capecitabine)
arm group label: Arm B: (start levocetirizine before bevacizumab/capecitabine)
other name: Xeloda®
intervention type: Drug
intervention name: Levocetirizine
arm group label: Arm A: (start levocetirizine after bevacizumab/capecitabine)
arm group label: Arm B: (start levocetirizine before bevacizumab/capecitabine)
other name: Xyzal
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Manik A Amin, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Bevacizumab
mesh term: Capecitabine
mesh term: Levocetirizine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 