<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/NCT02248571</url>
  </required_header>
  <id_info>
    <org_study_id>iOM-12293</org_study_id>
    <nct_id>NCT02248571</nct_id>
  </id_info>
  <brief_title>Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab</brief_title>
  <acronym>IMPROVE</acronym>
  <official_title>An Open Label, randomIzed Controlled Prospective Multicenter Two Arm Phase IV Trial to Determine Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab for Advanced (Inoperable or Metastatic) HER2-negative Hormone Receptor Positive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>iOMEDICO AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Arbeitsgemeinschaft fur Internistische Onkologie</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>iOMEDICO AG</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a clinical trial with a crossover design to determine patients' preference for&#xD;
      capecitabine in combination with bevacizumab or everolimus in combination with exemestane for&#xD;
      advanced breast cancer patients and to evaluate, if any combination is associated with a&#xD;
      better quality of life.&#xD;
&#xD;
      To identify patients' preference for either therapy in this trial, patients without disease&#xD;
      progression or other reasons for early discontinuation will be asked for their treatment&#xD;
      preference and their treatment satisfaction. To correlate patients' preference with other&#xD;
      patient reported outcomes (PROs), quality of life (QoL) will be assessed at baseline and&#xD;
      throughout the study, using dedicated questionnaires.&#xD;
&#xD;
      With similarly active treatment options, it is of utmost importance to identify the treatment&#xD;
      that has the least negative impact on the patients' quality of life.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">September 30, 2017</completion_date>
  <primary_completion_date type="Actual">August 31, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Patients' preference</measure>
    <time_frame>After 12 weeks of second treatment phase or two weeks after early (&lt; 12 weeks) treatment discontinuation</time_frame>
    <description>Patients' preference of the two treatment combinations capecitabine plus bevacizumab or everolimus in combination with exemestane after failure of standard antihormonal therapy in patients with advanced (inoperable or metastatic) HER2/neu-negative hormone receptor positive breast cancer.&#xD;
The preference will be ascertained using the patient preference questionnaire.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reasons for patients' preference</measure>
    <time_frame>After 12 weeks of second treatment phase or two weeks after early (&lt; 12 weeks) treatment discontinuation</time_frame>
    <description>To evaluate reasons for preference as assessed by the patient preference questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported treatment satisfaction</measure>
    <time_frame>After 12 weeks of first and second treatment phase or two weeks after early (&lt; 12 weeks) treatment discontinuation of each treatment phase</time_frame>
    <description>To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>At baseline and after 12 weeks of first and second treatment phase or two weeks after early (&lt; 12 weeks) treatment discontinuation of each treatment phase</time_frame>
    <description>To investigate differences in quality of life by the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC QLQ-C30) and EORTC QLQ-FA13 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival rate</measure>
    <time_frame>After 12 weeks of first and second treatment phase</time_frame>
    <description>To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)</measure>
    <time_frame>Participants will be followed for the whole duration of first phase therapy, with an expected average of 12 months, plus 3 months of second phase therapy (15 months in total)</time_frame>
    <description>To assess clinical benefit by determining objective response rates and disease control rates based on tumor assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities</measure>
    <time_frame>From date of informed consent to +30 days from last application of study medication</time_frame>
    <description>To evaluate safety and tolerability throughout the study according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.03 criteria, including clinical laboratory (grades 3 or 4 - separately for hematology and biochemistry) and number of treatment-emergent AEs (safety data for pre- and post-treatment periods will be listed separately)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physicians' treatment preference</measure>
    <time_frame>After 12 weeks of second treatment phase or two weeks after early (&lt; 12 weeks) treatment discontinuation</time_frame>
    <description>To determine physicians' treatment preference as assessed by the physician preference questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival for first and second treatment phase</measure>
    <time_frame>Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)</time_frame>
    <description>To explore progression free survival separately for each treatment phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Participants will be followed until death (expected median of 24 months)</time_frame>
    <description>To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Relationship Quality of life scores / patient preference</measure>
    <time_frame>At baseline and after 12 weeks of first and second treatment phase or two weeks after early (&lt; 12 weeks) treatment discontinuation of each treatment phase</time_frame>
    <description>To explore relationship between QoL scores and patient preference (Exploratory objective)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">85</enrollment>
  <condition>Breast Cancer Recurrent</condition>
  <condition>HER2/Neu-negative Carcinoma of Breast</condition>
  <condition>Hormone Receptor Positive Malignant Neoplasm of Breast</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)&#xD;
Dosing (treatment cycle: 21days):&#xD;
Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent)&#xD;
Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet&#xD;
Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)&#xD;
Dosing (treatment cycle: 21days):&#xD;
Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet&#xD;
Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent)&#xD;
Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>administered as combined therapy with Capecitabine</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Avastin®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>administered as combined therapy with Bevacizumab</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>administered as combined therapy with Exemestane</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Afinitor®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane</intervention_name>
    <description>administered as combined therapy with Everolimus</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Patient questionaires</intervention_name>
    <description>Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Papient reported outcome</other_name>
    <other_name>Patients' preference</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Written informed consent must be obtained prior to any study specific procedure.&#xD;
&#xD;
          1. Adult women (≥ 18 years of age)&#xD;
&#xD;
          2. . Postmenopausal status&#xD;
&#xD;
             The investigator must confirm postmenopausal status. Postmenopausal status is defined&#xD;
             either by:&#xD;
&#xD;
               -  Age ≥ 55 years and one year or more of amenorrhea&#xD;
&#xD;
               -  Age &lt; 55 years and one year or more of amenorrhea and postmenopausal levels of&#xD;
                  follicle stimulating hormone (FSH) and Luteinizing hormone (LH) per local&#xD;
                  institutional standards&#xD;
&#xD;
               -  Prior hysterectomy and has postmenopausal levels of FSH and LH per local&#xD;
                  institutional standards&#xD;
&#xD;
               -  Surgical menopause with bilateral oophorectomy&#xD;
&#xD;
               -  For women with therapy-induced amenorrhea, oophorectomy or serial measurements of&#xD;
                  FSH and / or estradiol are needed to ensure postmenopausal status.&#xD;
&#xD;
             Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone&#xD;
             (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for&#xD;
             induction of ovarian suppression.&#xD;
&#xD;
          3. Pathologically confirmed HER2/neu-negative, ER/PR positive inoperable or metastatic&#xD;
             adenocarcinoma of the breast&#xD;
&#xD;
          4. Indication for systemic palliative targeted therapy / first line chemotherapy after&#xD;
             failure of at least one non-steroidal aromatase inhibitor therapy at any time during&#xD;
             the disease course (no restriction regarding the number of previous endocrine lines)&#xD;
&#xD;
          5. No indication for other chemotherapeutic treatment including Taxanes or Anthracyclines&#xD;
&#xD;
          6. Measurable or non-measurable disease as per RECIST 1.1&#xD;
&#xD;
          7. Adequate bone marrow, liver and renal function (according to current SmPCs of both&#xD;
             treatment regimens)&#xD;
&#xD;
          8. ECOG performance status 0-2&#xD;
&#xD;
          9. Fluent German (spoken and written) language&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior palliative cytotoxic chemotherapies&#xD;
&#xD;
          2. Prior exposure to mTOR-Inhibitors (prior treatment with exemestane is allowed)&#xD;
&#xD;
          3. Concomitant antihormonal therapies, other than study medication&#xD;
&#xD;
          4. Symptomatic visceral metastases (as deemed by the investigator)&#xD;
&#xD;
          5. Uncontrolled CNS metastases&#xD;
&#xD;
          6. Unstable skeletal metastases&#xD;
&#xD;
          7. Medically uncontrolled cardiovascular diseases (e.g. uncontrolled hypertension)&#xD;
&#xD;
          8. Medically uncontrolled diabetes mellitus&#xD;
&#xD;
          9. Severe hepatic impairment (Child-Pugh C)&#xD;
&#xD;
         10. Inadequate organ function as specified below:&#xD;
&#xD;
               -  Hemoglobin &lt; 9.0 g/dl&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &lt;1,5 x109/L&#xD;
&#xD;
               -  Platelets &lt;100 x109/L&#xD;
&#xD;
               -  Creatinine clearance &lt; 30ml/min [Cockcroft and Gault]&#xD;
&#xD;
         11. Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C&#xD;
&#xD;
         12. Known dihydropyrimidine dehydrogenase (DPD) deficiency&#xD;
&#xD;
         13. Any other contraindications to the study drugs used or their excipients according to&#xD;
             current SmPCs&#xD;
&#xD;
         14. Concomitant use of immunosuppressive agents or chronic use of systemic corticosteroids&#xD;
&#xD;
         15. Use of any other concomitant medication known to interfere with the study drugs&#xD;
&#xD;
         16. Use of concomitant medication known to interfere with the study results (e.g. hormonal&#xD;
             therapy) during the whole study duration&#xD;
&#xD;
         17. Premenopausal patients&#xD;
&#xD;
         18. Pregnant or breast feeding patients&#xD;
&#xD;
         19. Participation in additional parallel interventional drug or device studies within four&#xD;
             weeks before start of study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Decker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>practice based oncology office Ravensburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>iOMEDICO AG</name>
      <address>
        <city>Freiburg</city>
        <state>Baden-Wuerttemberg</state>
        <zip>79108</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.</citation>
    <PMID>22149876</PMID>
  </reference>
  <reference>
    <citation>Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. doi: 10.1007/s12325-013-0060-1. Epub 2013 Oct 25. Erratum In: Adv Ther. 2014 Sep;31(9):1008-9.</citation>
    <PMID>24158787</PMID>
  </reference>
  <reference>
    <citation>Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. doi: 10.1200/JCO.2005.05.098.</citation>
    <PMID>15681523</PMID>
  </reference>
  <reference>
    <citation>Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.</citation>
    <PMID>21383283</PMID>
  </reference>
  <reference>
    <citation>Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Negrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. doi: 10.1200/JCO.2013.50.8267. Epub 2014 Mar 31.</citation>
    <PMID>24687826</PMID>
  </reference>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>November 8, 2017</last_update_submitted>
  <last_update_submitted_qc>November 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>breast cancer</keyword>
  <keyword>advanced</keyword>
  <keyword>inoperable</keyword>
  <keyword>metastatic</keyword>
  <keyword>HER2/neu-negative</keyword>
  <keyword>hormone receptor positive</keyword>
  <keyword>HR+</keyword>
  <keyword>female</keyword>
  <keyword>postmenopausal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>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>Everolimus</mesh_term>
    <mesh_term>Exemestane</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02248571
org study id: iOM-12293
nct id: NCT02248571
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
This is a clinical trial with a crossover design to determine patients' preference for
      capecitabine in combination with bevacizumab or everolimus in combination with exemestane for
      advanced breast cancer patients and to evaluate, if any combination is associated with a
      better quality of life.

      To identify patients' preference for either therapy in this trial, patients without disease
      progression or other reasons for early discontinuation will be asked for their treatment
      preference and their treatment satisfaction. To correlate patients' preference with other
      patient reported outcomes (PROs), quality of life (QoL) will be assessed at baseline and
      throughout the study, using dedicated questionnaires.

      With similarly active treatment options, it is of utmost importance to identify the treatment
      that has the least negative impact on the patients' quality of life.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Patients' preference
time frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
description: Patients' preference of the two treatment combinations capecitabine plus bevacizumab or everolimus in combination with exemestane after failure of standard antihormonal therapy in patients with advanced (inoperable or metastatic) HER2/neu-negative hormone receptor positive breast cancer.
The preference will be ascertained using the patient preference questionnaire.
measure: Reasons for patients' preference
time frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
description: To evaluate reasons for preference as assessed by the patient preference questionnaire
measure: Patient reported treatment satisfaction
time frame: After 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
description: To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase
measure: Quality of life
time frame: At baseline and after 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
description: To investigate differences in quality of life by the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC QLQ-C30) and EORTC QLQ-FA13 questionnaire
measure: Progression free survival rate
time frame: After 12 weeks of first and second treatment phase
description: To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)
measure: Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)
time frame: Participants will be followed for the whole duration of first phase therapy, with an expected average of 12 months, plus 3 months of second phase therapy (15 months in total)
description: To assess clinical benefit by determining objective response rates and disease control rates based on tumor assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
measure: Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities
time frame: From date of informed consent to +30 days from last application of study medication
description: To evaluate safety and tolerability throughout the study according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.03 criteria, including clinical laboratory (grades 3 or 4 - separately for hematology and biochemistry) and number of treatment-emergent AEs (safety data for pre- and post-treatment periods will be listed separately)
measure: Physicians' treatment preference
time frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
description: To determine physicians' treatment preference as assessed by the physician preference questionnaire
measure: Progression free survival for first and second treatment phase
time frame: Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)
description: To explore progression free survival separately for each treatment phase
measure: Overall survival
time frame: Participants will be followed until death (expected median of 24 months)
description: To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase
measure: Relationship Quality of life scores / patient preference
time frame: At baseline and after 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
description: To explore relationship between QoL scores and patient preference (Exploratory objective)
arm group label: Arm A
arm group type: Experimental
description: Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase)
Dosing (treatment cycle: 21days):
Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent)
Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)
arm group label: Arm B
arm group type: Experimental
description: Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase)
Dosing (treatment cycle: 21days):
Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet
Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent)
Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)
intervention type: Drug
intervention name: Bevacizumab
description: administered as combined therapy with Capecitabine
arm group label: Arm A
arm group label: Arm B
other name: Avastin®
intervention type: Drug
intervention name: Capecitabine
description: administered as combined therapy with Bevacizumab
arm group label: Arm A
arm group label: Arm B
intervention type: Drug
intervention name: Everolimus
description: administered as combined therapy with Exemestane
arm group label: Arm A
arm group label: Arm B
other name: Afinitor®
intervention type: Drug
intervention name: Exemestane
description: administered as combined therapy with Everolimus
arm group label: Arm A
arm group label: Arm B
intervention type: Other
intervention name: Patient questionaires
description: Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
arm group label: Arm A
arm group label: Arm B
other name: Papient reported outcome
other name: Patients' preference
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Decker, MD
role: Principal Investigator
affiliation: practice based oncology office Ravensburg
facility: 
country: Germany
citation: Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.
PMID: 22149876
citation: Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. doi: 10.1007/s12325-013-0060-1. Epub 2013 Oct 25. Erratum In: Adv Ther. 2014 Sep;31(9):1008-9.
PMID: 24158787
citation: Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. doi: 10.1200/JCO.2005.05.098.
PMID: 15681523
citation: Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.
PMID: 21383283
citation: Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Negrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. doi: 10.1200/JCO.2013.50.8267. Epub 2014 Mar 31.
PMID: 24687826
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Neoplasms
mesh term: Bevacizumab
mesh term: Capecitabine
mesh term: Everolimus
mesh term: Exemestane
sharing ipd: No