<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/NCT01733628</url>
  </required_header>
  <id_info>
    <org_study_id>GEICAM/2011-04</org_study_id>
    <secondary_id>GEI-BEV-2011-02</secondary_id>
    <nct_id>NCT01733628</nct_id>
  </id_info>
  <brief_title>Evaluation of Hypertension as a Predictor of Efficacy Bevacizumab in Metastatic Breast Cancer and Colorectal Cancer</brief_title>
  <acronym>BRECOL</acronym>
  <official_title>Evaluation Study of Hypertension as a Predictor of Efficacy Bevacizumab (BV) in Combination With Chemotherapy (CT) in Metastatic Colorectal Cancer (MCC) and Metastatic Breast Cancer (MBC).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spanish Breast Cancer Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Farma, S.A</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Spanish Breast Cancer Research Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, post-authorization observational with prospective follow-up (EPA-SP)&#xD;
      study. Will be involved 137 metastatic breast cancer patients or metastatic colorectal&#xD;
      cancer. The hypertension will be evaluated as a predictor of efficacy of bevacizumab&#xD;
      associated with chemotherapy, in terms of progression-free survival (PFS) (Main endpoint).&#xD;
&#xD;
      The duration of the study will be approximately 42 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypertension (HT) is the most common side effect seen in trials of bevacizumab in combination&#xD;
      with chemotherapy. Based on the hypothesis that the development of hypertension during&#xD;
      treatment would be an indicative of the successful blockade of the Vascular Endothelial&#xD;
      Growth Factor (VEGF) pathway, different studies have explored retrospectively the&#xD;
      relationship between hypertension and the results of treatment with bevacizumab.&#xD;
&#xD;
      This study aims to demonstrate the association between hypertension (diagnosed optimally)&#xD;
      with efficacy to treatment with bevacizumab prospectively and secondly verify if blood&#xD;
      pressure measures taken at home are a reflection of a diagnosis of hypertension.&#xD;
&#xD;
      Also have been explored different molecular markers involved in the pathway of VEGF which&#xD;
      might be used as predictors of response. Therefore, this study includes the collection of&#xD;
      blood samples (serum or plasma) and tumor tissue of patients included in this study, with the&#xD;
      aim of exploring biomarkers that correlate with treatment efficacy and toxicity.&#xD;
&#xD;
      The diagnosis of hypertension (HT) will be performed using a Holter recording, and standard&#xD;
      blood pressure footage will be collected during the first three cycles of treatment given the&#xD;
      Common Toxicity Criteria of the National Cancer Institute-NCI CTCAE version 4.0 and the&#xD;
      guidelines of the European Society of Cardiology and Hypertension, 2007.&#xD;
&#xD;
      Will be collected a sample of primary tumor and blood for patients who previously have&#xD;
      consented it. Samples will be sent to a central laboratory for analysis of biomarkers.&#xD;
&#xD;
      An interim analysis will be conducted to assess the true incidence of hypertension. Based on&#xD;
      this analysis, will be evaluated the need to recalculate the sample size.&#xD;
&#xD;
      At the end of the study, will be performed an analysis of correlation of data measured by&#xD;
      standard BP (Blood Pressure) and Holter recording footage with the PFS. Moreover will be&#xD;
      determined in serum, plasma and tumor tissue and certain biomarkers to correlate with&#xD;
      efficacy to treatment with bevacizumab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2012</start_date>
  <completion_date type="Actual">December 19, 2017</completion_date>
  <primary_completion_date type="Actual">December 19, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With &quot;White Coat&quot; AHT While at Home</measure>
    <time_frame>Cycle 1, cycle 2, and cycle 3, up to 9 weeks</time_frame>
    <description>The incidence of &quot;white coat&quot; arterial hypertension (AHT) was evaluated comparing each of the measurements in medical attention (in a doctor office) with the measurement that was made at home (without a doctor).&#xD;
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With &quot;White Coat&quot; AHT With 24 Hours Ambulatory BP Measure</measure>
    <time_frame>Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks</time_frame>
    <description>The incidence of &quot;white coat&quot; arterial hypertension (AHT) was evaluated comparing each of the measurements with the measurement that was made in the hospital. Ambulatory Blood Pressure Monitoring (ABPM) is when the blood pressure is being measured as patient moves around, living her normal daily life.&#xD;
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">143</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Bevacizumab + Chemotherapy</arm_group_label>
    <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples (serum or plasma) Tissue samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with metastatic (disseminated at the time of diagnosis) breast cancer or&#xD;
        colorectal cancer, treated with bevacizumab.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        May only participate in the study patients (women and men) who meet all the following&#xD;
        criteria:&#xD;
&#xD;
          1. MCC or MBC patients with chemotherapy and bevacizumab established indication. The&#xD;
             first line systemic treatment planned for patients with MCC should be based in&#xD;
             combination chemotherapy (oxaliplatin / irinotecan plus fluoropyrimidine) associated&#xD;
             with bevacizumab. The first line systemic treatment planned for MBC patients should be&#xD;
             based on a combination of paclitaxel or capecitabine plus bevacizumab.&#xD;
&#xD;
          2. Presence of measurable or evaluable disease according to RECIST 1.1, for the&#xD;
             evaluation of the response to treatment.&#xD;
&#xD;
          3. Equal or more than 18 years old.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          5. Signed written informed consent.&#xD;
&#xD;
          6. Women of childbearing potential must have a negative pregnancy test in serum or urine&#xD;
             conducted in the 7 days prior to the administration of chemotherapeutic treatment&#xD;
             assigned by your doctor, and accept the use of double barrier contraception during the&#xD;
             study (Note : Patients who are not of childbearing age may participate without using&#xD;
             contraceptives. Women who are of childbearing age are those who: 1) have reached&#xD;
             natural menopause (defined as 6 months of spontaneous amenorrhea with serum&#xD;
             follicle-stimulating hormone (FSH) within postmenopausal interval as determined by the&#xD;
             laboratory, or 12 months of spontaneous amenorrhea), 2) have undergone bilateral&#xD;
             oophorectomy with or without hysterectomy 6 weeks before, or 3) have undergone&#xD;
             bilateral tubal ligation). Men also should use an adequate contraception method.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients meeting any of the following circumstances will be excluded from the study:&#xD;
&#xD;
          1. Have received prior systemic anticancer therapy with chemotherapy for advanced disease&#xD;
             or prior treatment with bevacizumab.&#xD;
&#xD;
          2. Treatment with an investigational agent or biological agent within 30 days prior to&#xD;
             inclusion in the study.&#xD;
&#xD;
          3. Contraindications to treatment with chemotherapy and bevacizumab according to summary&#xD;
             products characteristics.&#xD;
&#xD;
          4. Background or current history (within five years before the start of treatment) of&#xD;
             other malignancies, except for colorectal carcinoma and breast cancer (patients with&#xD;
             basal cell carcinoma or squamous cell skin or cervical carcinoma in situ treated&#xD;
             curative may be included in the study).&#xD;
&#xD;
          5. Life expectancy less than 3 months.&#xD;
&#xD;
          6. Patients who are pregnant or breastfeeding.&#xD;
&#xD;
          7. Patients with an inadequate organ function (bone marrow, kidney and liver)&#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>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Hospital General Universitario de Elche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital General Universitario de Elche</name>
      <address>
        <city>Elche</city>
        <state>Alicante</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario A Coruña</name>
      <address>
        <city>A Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Alicante</name>
      <address>
        <city>Alicante</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario Reina Sofía</name>
      <address>
        <city>Córdoba</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Jaén</name>
      <address>
        <city>Jaén</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Oncológico MD Anderson</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Fe</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.geicam.org/</url>
    <description>Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group</description>
  </link>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>June 6, 2019</results_first_submitted>
  <results_first_submitted_qc>December 3, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 4, 2019</results_first_posted>
  <last_update_submitted>December 3, 2019</last_update_submitted>
  <last_update_submitted_qc>December 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypertension</keyword>
  <keyword>Bevacizumab Response Predictors</keyword>
  <keyword>Metastatic Breast Cancer</keyword>
  <keyword>Metastatic Colon Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 23, 2012</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT01733628/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>From October 2012 to July 2016, 143 patients were included.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Bevacizumab + Chemotherapy</title>
          <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="143"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="143"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bevacizumab + Chemotherapy</title>
          <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="143"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.18" lower_limit="32.57" upper_limit="85.32"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="102"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Spain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) status</title>
          <description>ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. 0 - Asymptomatic&#xD;
- Symptomatic but completely ambulatory&#xD;
- Symptomatic, &lt;50% in bed during the day&#xD;
- Symptomatic, &gt;50% in bed, but not bedbound&#xD;
- Bedbound&#xD;
- Death</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>ECOG 0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ECOG 1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="72"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Blood Pressure Systolic</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="129.4" lower_limit="80" upper_limit="216"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Blood Pressure Diastolic</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.73" lower_limit="50" upper_limit="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pulse</title>
          <units>bpm</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78.92" lower_limit="52" upper_limit="128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Women Menopausal Status</title>
          <population>Only women were assessed for this measure</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Postmenopausal women</title>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Premenopausal women</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Previous arterial hypertension</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Previous arterial hypertension</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Previous arterial hypertension</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cancer type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Metastatic Colorectal Cancer (MCRC)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Metastatic Breast Cancer (MBC)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)</title>
        <description>The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).</description>
        <time_frame>Up to 3 years</time_frame>
        <population>There were 30 patients who were not included in Population per Protocol because of the following: 6 patients didn't fulfil inclusion and exclusion criteria, 8 patients didn't received Bevacizumab, 16 patients didn't have Holter assessment performed at baseline and/or at any other study visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab + Chemotherapy</title>
            <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)</title>
          <description>The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).</description>
          <population>There were 30 patients who were not included in Population per Protocol because of the following: 6 patients didn't fulfil inclusion and exclusion criteria, 8 patients didn't received Bevacizumab, 16 patients didn't have Holter assessment performed at baseline and/or at any other study visit.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No AHT : 0 to 0.5 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No AHT : 0.5 to 1 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No AHT : 1 to 1.5 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No AHT : 1.5 to 2 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No AHT : 2 to 2.5 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No AHT: 2.5 to 3 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes AHT: 0 to 0.5 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes AHT: 0.5 to 1 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes AHT: 1 to 1.5 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes AHT: 1.5 to 2 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes AHT: 2 to 2.5 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes AHT: 2.5 to 3 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Type of statistical Test: Inequality</non_inferiority_desc>
            <p_value>0.8166</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.94</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.56</ci_lower_limit>
            <ci_upper_limit>1.59</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>There were 30 patients who were not included in Population per Protocol because of the following: 6 patients didn't fulfil inclusion and exclusion criteria, 8 patients didn't received Bevacizumab, 16 patients didn't have Holter assessment performed at baseline and/or at any other study visit</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab + Chemotherapy</title>
            <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <population>There were 30 patients who were not included in Population per Protocol because of the following: 6 patients didn't fulfil inclusion and exclusion criteria, 8 patients didn't received Bevacizumab, 16 patients didn't have Holter assessment performed at baseline and/or at any other study visit</population>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.19" spread="8.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With &quot;White Coat&quot; AHT While at Home</title>
        <description>The incidence of &quot;white coat&quot; arterial hypertension (AHT) was evaluated comparing each of the measurements in medical attention (in a doctor office) with the measurement that was made at home (without a doctor).&#xD;
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.</description>
        <time_frame>Cycle 1, cycle 2, and cycle 3, up to 9 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab + Chemotherapy</title>
            <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With &quot;White Coat&quot; AHT While at Home</title>
          <description>The incidence of &quot;white coat&quot; arterial hypertension (AHT) was evaluated comparing each of the measurements in medical attention (in a doctor office) with the measurement that was made at home (without a doctor).&#xD;
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>White coat AHT in cycle 1</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White coat AHT in cycle 2</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White coat AHT in cycle 3</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With &quot;White Coat&quot; AHT With 24 Hours Ambulatory BP Measure</title>
        <description>The incidence of &quot;white coat&quot; arterial hypertension (AHT) was evaluated comparing each of the measurements with the measurement that was made in the hospital. Ambulatory Blood Pressure Monitoring (ABPM) is when the blood pressure is being measured as patient moves around, living her normal daily life.&#xD;
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.</description>
        <time_frame>Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab + Chemotherapy</title>
            <description>Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With &quot;White Coat&quot; AHT With 24 Hours Ambulatory BP Measure</title>
          <description>The incidence of &quot;white coat&quot; arterial hypertension (AHT) was evaluated comparing each of the measurements with the measurement that was made in the hospital. Ambulatory Blood Pressure Monitoring (ABPM) is when the blood pressure is being measured as patient moves around, living her normal daily life.&#xD;
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>White coat AHT in baseline</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="94"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White coat AHT in cycle 1</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White coat AHT in cycle 2</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White coat AHT in cycle 3</title>
              <category_list>
                <category>
                  <title>No AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Yes AHT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events occurred during the treatment and up to 30 days after the last dose were notified. All Serious Adverse Events (SAEs) that occurred within the first 3 cycles were recorded in the electronic Case Report Form (eCRF). Only those Grade 3-4 adverse events that were related to the treatment that occurred during the first 3 treatment cycles were recorded in the eCRF.</time_frame>
      <desc>The Safety Population (SP) included 135 patients who signed the Informed Consent and received at least 1 dose of Chemotherapy combined with Bevacizumab.&#xD;
The Intent to Treat (ITT) Population included 143 patients who signed the Informed Consent.&#xD;
Serious Adverse Events and/or Other (Not Including Serious) Adverse Events (AEs) have been calculated in the SP (n=135), and All-Cause Mortality have been calculated in the ITT population (n=143) as per protocol.</desc>
      <group_list>
        <group group_id="E1">
          <title>Bevacizumab + Chemotherapy</title>
          <description>The Safety Population (SP) included 135 patients who signed the Informed Consent and received at least 1 dose of Chemotherapy combined with Bevacizumab.&#xD;
The Intent to Treat (ITT) Population included 143 patients who signed the Informed Consent.&#xD;
Serious Adverse Events and/or Other (Not Including Serious) Adverse Events (AEs) have been calculated in the SP (n=135), and All-Cause Mortality have been calculated in the ITT population (n=143).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>NCI-CTC v. 4.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="143"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>ICTUS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Skin infection: Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Lynph Gland Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Penile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </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="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </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="2" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Coronary Angiography</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>NCI-CTC v. 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="57" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <description>Grade 4</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <description>Grade 4</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Grade 4</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Fistulized perianal abscess</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>GGT increased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>APTT increased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>LDL Cholesterol increased</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <description>Grade 4</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
              <event>
                <sub_title>Rash/Desquamation</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="135"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Scientific Director / Medical Lead / Project Manager</name_or_title>
      <organization>Spanish Breast Cancer Research Group</organization>
      <phone>+34916592870</phone>
      <email>geicam@geicam.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01733628
org study id: GEICAM/2011-04
secondary id: GEI-BEV-2011-02
nct id: NCT01733628
lead sponsor: 
collaborator: 
has dmc: No
This is a multicenter, post-authorization observational with prospective follow-up (EPA-SP)
      study. Will be involved 137 metastatic breast cancer patients or metastatic colorectal
      cancer. The hypertension will be evaluated as a predictor of efficacy of bevacizumab
      associated with chemotherapy, in terms of progression-free survival (PFS) (Main endpoint).

      The duration of the study will be approximately 42 months.
Hypertension (HT) is the most common side effect seen in trials of bevacizumab in combination
      with chemotherapy. Based on the hypothesis that the development of hypertension during
      treatment would be an indicative of the successful blockade of the Vascular Endothelial
      Growth Factor (VEGF) pathway, different studies have explored retrospectively the
      relationship between hypertension and the results of treatment with bevacizumab.

      This study aims to demonstrate the association between hypertension (diagnosed optimally)
      with efficacy to treatment with bevacizumab prospectively and secondly verify if blood
      pressure measures taken at home are a reflection of a diagnosis of hypertension.

      Also have been explored different molecular markers involved in the pathway of VEGF which
      might be used as predictors of response. Therefore, this study includes the collection of
      blood samples (serum or plasma) and tumor tissue of patients included in this study, with the
      aim of exploring biomarkers that correlate with treatment efficacy and toxicity.

      The diagnosis of hypertension (HT) will be performed using a Holter recording, and standard
      blood pressure footage will be collected during the first three cycles of treatment given the
      Common Toxicity Criteria of the National Cancer Institute-NCI CTCAE version 4.0 and the
      guidelines of the European Society of Cardiology and Hypertension, 2007.

      Will be collected a sample of primary tumor and blood for patients who previously have
      consented it. Samples will be sent to a central laboratory for analysis of biomarkers.

      An interim analysis will be conducted to assess the true incidence of hypertension. Based on
      this analysis, will be evaluated the need to recalculate the sample size.

      At the end of the study, will be performed an analysis of correlation of data measured by
      standard BP (Blood Pressure) and Holter recording footage with the PFS. Moreover will be
      determined in serum, plasma and tumor tissue and certain biomarkers to correlate with
      efficacy to treatment with bevacizumab.
observational model: Case-Only
time perspective: Prospective
measure: Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)
time frame: Up to 3 years
description: The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).
measure: Progression Free Survival (PFS)
time frame: Up to 3 years
description: The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Number of Participants With "White Coat" AHT While at Home
time frame: Cycle 1, cycle 2, and cycle 3, up to 9 weeks
description: The incidence of "white coat" arterial hypertension (AHT) was evaluated comparing each of the measurements in medical attention (in a doctor office) with the measurement that was made at home (without a doctor).
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.
measure: Number of Participants With "White Coat" AHT With 24 Hours Ambulatory BP Measure
time frame: Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks
description: The incidence of "white coat" arterial hypertension (AHT) was evaluated comparing each of the measurements with the measurement that was made in the hospital. Ambulatory Blood Pressure Monitoring (ABPM) is when the blood pressure is being measured as patient moves around, living her normal daily life.
White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.
arm group label: Bevacizumab + Chemotherapy
description: Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.
Blood samples (serum or plasma) Tissue samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Hospital General Universitario de Elche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
url: http://www.geicam.org/
description: Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Hypertension
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 