<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/NCT01722968</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT no: 2012-003743-30</org_study_id>
    <nct_id>NCT01722968</nct_id>
  </id_info>
  <brief_title>A Biomarker Study in Patients With HER2-negative Metastatic Breast Cancer Treated With Bevacizumab and Paclitaxel</brief_title>
  <acronym>BEVPAC</acronym>
  <official_title>A Prospective Randomized Phase II Study to Identify Predictive Biomarkers and Mechanisms of Therapy Resistance in Patients With HER2-negative Metastatic Breast Cancer Treated With the Combination of Bevacizumab and Paclitaxel (BEVPAC).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Theodoros Foukakis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To explore molecular biomarkers and/or gene expression signatures that predict response to&#xD;
      bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative&#xD;
      metastatic breast cancer (MBC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, randomized, 2-arm, open-label, single-center, phase II trial. A total&#xD;
      of 30 patients will be included during a period of 2 years.&#xD;
&#xD;
      The study will be initiated with a non-randomized, feasibility stage including ten patients&#xD;
      who will be treated with bevacizumab and paclitaxel, in order to determine the safety of&#xD;
      metastatic tumor biopsies during therapy with bevacizumab.&#xD;
&#xD;
      In the second phase, patients will be randomized (1:1) between two treatment arms: A.&#xD;
      Bevacizumab + paclitaxel and B. Paclitaxel&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <primary_completion_date type="Actual">June 2018</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>Identification of molecular biomarkers</measure>
    <time_frame>After the study completion,After completion of the study, which will take up to 3 years</time_frame>
    <description>To explore molecular biomarkers and/or gene expression signatures that predict response to bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative MBC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of metastatic biopsies during bevacizumab therapy</measure>
    <time_frame>continuous assessment and after inclusion of 10 patients, After completion of the study which will take up to 1 year</time_frame>
    <description>The safety objective of the study is to assess whether carrying out metastatic tissue biopsies during treatment with bevacizumab is safe. For this reason, the study will be initiated with a feasibility phase of 10 patients and will be continued to the randomized phase only if the study specific procedures prove to be safe.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Molecular changes by bevacizumab</measure>
    <time_frame>After completion of the study which will take up to 3 years</time_frame>
    <description>To identify molecular changes in the tumor induced by the addition of bevacizumab to chemotherapy.</description>
  </other_outcome>
  <other_outcome>
    <measure>Efficacy of bevacizumab</measure>
    <time_frame>After completion of the study, After completion of the study, which will take up to 3 years</time_frame>
    <description>To measure the efficacy of bevacizumab in combination with paclitaxel in HER2 negative MBC.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Arm A and feasibility phase: Bevacizumab 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Arm B: Paclitaxel 80mg/m2 iv weekly.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>80mg/m2 iv weekly</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Paxene</other_name>
    <other_name>Taxol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-70 years.&#xD;
&#xD;
          2. Performance status ECOG 0-2.&#xD;
&#xD;
          3. Clinically and / or radiologically proven stage IV or recurrent HER2 negative breast&#xD;
             cancer.&#xD;
&#xD;
          4. At least one tumor lesion accessible for biopsy. This lesion may not have been treated&#xD;
             previously with irradiation.&#xD;
&#xD;
          5. Clinically and/or radiographically documented measurable disease according to RECIST&#xD;
             v1.1 criteria. At least one site of disease must be unidimensionally measurable as&#xD;
             follows:&#xD;
&#xD;
               1. CT-scan, physical exam ≥ 10 mm} Chest X-ray ≥ 20 mm }see Eisenhauer et al. for&#xD;
                  more details&#xD;
&#xD;
               2. Lymph node short axis ≥ 15 mm }&#xD;
&#xD;
               3. All radiology studies must be performed within 28 days prior to registration (35&#xD;
                  days if negative).&#xD;
&#xD;
          6. Adequate bone-marrow, hepatic and renal function defined as laboratory tests within 7&#xD;
             days prior to enrollment:&#xD;
&#xD;
               1. Haematology: Absolute granulocytes &gt; 1.5 x 109/L Platelets &gt; 100 x 109/L&#xD;
&#xD;
               2. Biochemistry:Bilirubin within normal limits Serum creatinine within normal limits&#xD;
&#xD;
          7. APTT and INR within normal limits within 7 days prior to enrollment.&#xD;
&#xD;
          8. Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) within normal&#xD;
             limits determined by echocardiogram or MUGA within 28 days prior to inclusion.&#xD;
&#xD;
          9. Written informed consent must be given.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous systemic treatment for MBC.&#xD;
&#xD;
          2. Major surgery less than 28 days prior to enrollment.&#xD;
&#xD;
          3. Concurrent malignancy of any site, except adequately controlled limited basal cell&#xD;
             carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix.&#xD;
&#xD;
          4. Bleeding diathesis, history of thromboembolic disease, or ongoing treatment with&#xD;
             warfarin, heparin analogs or antiplatelet drugs.&#xD;
&#xD;
          5. Major cardiac comorbidity.&#xD;
&#xD;
          6. Previous treatment with bevacizumab.&#xD;
&#xD;
          7. Previous allergic reaction to taxane analogs.&#xD;
&#xD;
          8. Ongoing pregnancy or lactation.&#xD;
&#xD;
          9. Any psychological, familial, sociological or geographical condition potentially&#xD;
             hampering compliance with the study protocol and follow-up schedule; those conditions&#xD;
             should be discussed with the patient before registration in the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Theodoros Foukakis, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jonas Bergh, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Karolinska University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Solna</city>
        <state>Stockholm</state>
        <zip>17176</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>February 25, 2019</last_update_submitted>
  <last_update_submitted_qc>February 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Theodoros Foukakis</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Metastatic breast cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01722968
org study id: EudraCT no: 2012-003743-30
nct id: NCT01722968
lead sponsor: 
has dmc: Yes
To explore molecular biomarkers and/or gene expression signatures that predict response to
      bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative
      metastatic breast cancer (MBC).
This is a prospective, randomized, 2-arm, open-label, single-center, phase II trial. A total
      of 30 patients will be included during a period of 2 years.

      The study will be initiated with a non-randomized, feasibility stage including ten patients
      who will be treated with bevacizumab and paclitaxel, in order to determine the safety of
      metastatic tumor biopsies during therapy with bevacizumab.

      In the second phase, patients will be randomized (1:1) between two treatment arms: A.
      Bevacizumab + paclitaxel and B. Paclitaxel
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Identification of molecular biomarkers
time frame: After the study completion,After completion of the study, which will take up to 3 years
description: To explore molecular biomarkers and/or gene expression signatures that predict response to bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative MBC.
measure: Safety of metastatic biopsies during bevacizumab therapy
time frame: continuous assessment and after inclusion of 10 patients, After completion of the study which will take up to 1 year
description: The safety objective of the study is to assess whether carrying out metastatic tissue biopsies during treatment with bevacizumab is safe. For this reason, the study will be initiated with a feasibility phase of 10 patients and will be continued to the randomized phase only if the study specific procedures prove to be safe.
measure: Molecular changes by bevacizumab
time frame: After completion of the study which will take up to 3 years
description: To identify molecular changes in the tumor induced by the addition of bevacizumab to chemotherapy.
measure: Efficacy of bevacizumab
time frame: After completion of the study, After completion of the study, which will take up to 3 years
description: To measure the efficacy of bevacizumab in combination with paclitaxel in HER2 negative MBC.
arm group label: Arm A
arm group type: Active Comparator
description: Arm A and feasibility phase: Bevacizumab 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly.
arm group label: Arm B
arm group type: Active Comparator
description: Arm B: Paclitaxel 80mg/m2 iv weekly.
intervention type: Drug
intervention name: Bevacizumab
description: 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly
arm group label: Arm A
other name: Avastin
intervention type: Drug
intervention name: Paclitaxel
description: 80mg/m2 iv weekly
arm group label: Arm A
arm group label: Arm B
other name: Paxene
other name: Taxol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Theodoros Foukakis, MD PhD
role: Principal Investigator
affiliation: Karolinska University Hospital
last name: Jonas Bergh, Professor
role: Study Director
affiliation: Karolinska University Hospital
facility: 
country: Sweden
responsible party type: Sponsor-Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Theodoros Foukakis
investigator title: MD, PhD
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Bevacizumab