<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/NCT03007992</url>
  </required_header>
  <id_info>
    <org_study_id>2015-007</org_study_id>
    <nct_id>NCT03007992</nct_id>
  </id_info>
  <brief_title>Metronomic Treatment With Daily Oral Vinorelbine as First-line Chemotherapy in Patients With Advanced/Metastatic Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer</brief_title>
  <acronym>VinoMetro</acronym>
  <official_title>Phase II Study of Metronomic Treatment With Daily Oral Vinorelbine as First-line Chemotherapy in Patients With Advanced/Metastatic HR+/HER2- Breast Cancer Resistant to Endocrine Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johannes Gutenberg University Mainz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pierre Fabre Pharma GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Johannes Gutenberg University Mainz</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the trial is to investigate the efficacy of metronomic treatment with daily&#xD;
      oral vinorelbine in terms of clinical benefit rate based on local radiological assessment in&#xD;
      patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In terms of the chronic nature of advanced/metastatic breast cancer, there is a high medical&#xD;
      need for new treatment options after failure of hormonal treatment that prolong the interval&#xD;
      to the start of intensive cytotoxic therapy, which is commonly associated with impaired&#xD;
      quality of life (QoL) and potentially serious side effects. In this respect, metronomic&#xD;
      treatment with daily administration of oral vinorelbine could provide an efficacious&#xD;
      treatment option with limited toxicities.&#xD;
&#xD;
      Accordingly, this national, multi-centre, open-label, single-arm phase II trial aims to&#xD;
      investigate a truly metronomic schedule with daily oral vinorelbine in HR+/HER2-patients with&#xD;
      metastatic breast cancer resistant to endocrine therapy, by assessing efficacy and safety.&#xD;
      Oral vinorelbine will be administered at a daily dose of 30 mg (flat dose without any&#xD;
      adaptation to body weight or body surface area) without breaks. Treatment will continue until&#xD;
      disease progression, occurrence of unacceptable toxicity, patient's refusal or investigator's&#xD;
      decision to stop the treatment.&#xD;
&#xD;
      In the course of the study, the following interim and final analyses will be done:&#xD;
&#xD;
      i) 1st interim analysis (safety): This analysis will be performed on the basis of 10&#xD;
      patients, who were initially included into the study and who are eligible for safety&#xD;
      evaluation; frequency statistics of (serious) adverse events will be analysed.&#xD;
&#xD;
      ii) 2nd interim analysis (efficacy): This analysis will be performed at the completion of the&#xD;
      1st Simon stage.&#xD;
&#xD;
      iii) Final analysis (complete): This analysis will be performed after completion of the&#xD;
      follow-up phase (6 months of follow-up after Last Patient Last Treatment).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">March 2, 2019</completion_date>
  <primary_completion_date type="Actual">March 2, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>24 weeks after start of treatment.</time_frame>
    <description>The primary endpoint is the determination of the Clinical Benefit Rate (CBR) at 24 weeks after start of treatment. The response to treatment is measured by computer tomography (CT) or magnetic resonance imaging (MRI) for measurable lesions and evaluation for non-measurable lesions at 24 weeks after start of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of disease control (DoDC)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of stable disease (DoSD)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure (TTF)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Statistical evaluation of above mentioned parameter for each patient measured in duration of month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Determination of frequency and severity of (serious) adverse events and the number of laboratory values worsening from baseline based on the Common Toxicity Criteria (CTC) Grade; other safety data (e.g. vital signs and special tests) will be considered as appropriate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's symptoms and health-related quality of life</measure>
    <time_frame>6 months after last patient last treatment</time_frame>
    <description>Evaluation of the Global Health Status/QoL on the basis of the Eastern Cooperative Oncology Group (EORTC) quality of life questionnaire (QLQ)-C30 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histopathological parameters</measure>
    <time_frame>before start of treatment and upon progression, assessed up to 6 months after last patient last treatment</time_frame>
    <description>Analysis of tumour tissue biomarkers before the start of study treatment and upon progression: histopathological analyses including qualitative assessments of tumor-infiltrating lymphocytes (TIL) involving the evaluation of regulatory T cells (Treg), cluster of differentiation 8 (CD8), CD20 and immune checkpoint parameters (e.g. Programmed Death-Ligand 1 (PD-L1)); additionally, markers like vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and hypoxia inducible factor-1 (HIF-1) will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker profiles</measure>
    <time_frame>before start of treatment, during treatment period and upon progression, assessed up to 6 months after last patient last treatment</time_frame>
    <description>Analysis of blood biomarkers before the start of study treatment, during the treatment period and upon progression: assessment of blood biomarkers, such as CD4+ CD25+ Forkhead-Box-Protein P3 (FOXP3+) Treg, T and B lymphocytes, natural killer (NK) cells and monocytes, hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and to evaluate potential correlations of biomarker expression and clinical outcomes (response, PFS, OS)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Vinorelbine Oral</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Test product: Navelbine® 20 mg / 30 mg soft capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vinorelbine</intervention_name>
    <description>Oral vinorelbine will be administered at a daily dose of 30 mg (flat dose without any adaptation to body weight or body surface area) without breaks. Treatment will continue until disease progression, occurrence of unacceptable toxicity, patient's refusal or investigator's decision to stop the treatment.</description>
    <arm_group_label>Vinorelbine Oral</arm_group_label>
    <other_name>Navelbine® soft capsules</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written (personally dated and signed) informed consent prior to the performance of any&#xD;
             trial specific procedure&#xD;
&#xD;
          2. Absence of any psychological, familial, sociological or geographical condition&#xD;
             potentially hampering compliance with the study protocol and/or the follow-up schedule&#xD;
&#xD;
          3. Female patient ≥ 18 years of age&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, which the&#xD;
             investigator assesses as being stable at time of screening&#xD;
&#xD;
          5. Estimated life expectancy ≥ 16 weeks&#xD;
&#xD;
          6. Histologically confirmed adenocarcinoma of the breast&#xD;
&#xD;
          7. Documented locally advanced or metastatic disease, previously untreated by palliative&#xD;
             chemotherapy and not amenable to any curative treatment&#xD;
&#xD;
          8. Hormone receptor positive disease determined by ≥ 1% positive stained cells for&#xD;
             oestrogen and/or progesterone receptor by immunohistochemistry on the primary tumour&#xD;
             or on a metastatic site&#xD;
&#xD;
          9. HER2-negative disease assessed by 0-1+ immuno-histochemistry (IHC) or 2+ IHC with&#xD;
             negative fluorescence in situ hybridization (FISH) or CISH) on the primary tumour or&#xD;
             on a metastatic site&#xD;
&#xD;
         10. Availability of archival (from the most recently obtained sample) or fresh tumour&#xD;
             tissue from patients included in the trial for the analysis of relevant metronomic&#xD;
             biomarkers; one tumour block (preferred) or a minimum of 12 (recommended: 15)&#xD;
             unstained slides to be provided&#xD;
&#xD;
         11. Relapse ≤ 12 months from end of adjuvant hormonal therapy or pro¬gres¬sion&#xD;
             during/after ≥ 1 line of endocrine therapy in the metastatic set¬ting and/or no longer&#xD;
             candidate for further endocrine therapy&#xD;
&#xD;
         12. Prior (neo-)adjuvant chemotherapy is allowed, if the interval between end of&#xD;
             chemotherapy and date of registration is &gt; 12 months&#xD;
&#xD;
         13. Prior treatment with everolimus and/or palbociclib in the frame of hormonal therapy is&#xD;
             allowed&#xD;
&#xD;
         14. Complete staging before registration (CT/MRI thorax and CT/MRI abdomen/pelvis ≤ 28&#xD;
             days before registration; bone scan ≤ 3 months before registration)&#xD;
&#xD;
         15. Presence of ≥ 1 measurable lesion as per RECIST 1.1, which has not been previously&#xD;
             irradiated&#xD;
&#xD;
         16. Adequate bone marrow, hepatic and renal function as defined by the following&#xD;
             laboratory values:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500/mm3&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mm3&#xD;
&#xD;
               -  Haemoglobin ≥ 10 g/dL&#xD;
&#xD;
               -  Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3 x ULN in case of&#xD;
                  liver metasta¬s¬es)&#xD;
&#xD;
               -  Liver transaminases ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metasta¬s¬es)&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 5 x ULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5 x ULN (creatinine clearance should be assessed based on the&#xD;
                  Cockcroft-Gault-formula in case of borderline values and should then be ≥ 50&#xD;
                  ml/min)&#xD;
&#xD;
         17. Women of childbearing potential must be using a medically accepted method of&#xD;
             contraception to avoid pregnancy during 2 months preceding registration, throughout&#xD;
             the study period and up to 3 months after last dose of study treatment in such a&#xD;
             manner that the risk of pregnancy is minimised; reliable contraception comprises&#xD;
             sexual abstinence, male sterilization or double barrier methods (e.g. a combination of&#xD;
             male condom with diaphragm).&#xD;
&#xD;
         18. Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             within 72 hours prior to start of study treatment&#xD;
&#xD;
         19. Ability of the patient to understand the character and the individual consequences of&#xD;
             this clinical trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. No recovery to ≤ Grade (G)1 side effects (exception: alopecia) of any prior&#xD;
             anti-neoplastic treatment&#xD;
&#xD;
          2. Aggressive locally advanced or metastatic breast cancer disease requiring systemic&#xD;
             combination therapy&#xD;
&#xD;
          3. Known or suspected central nervous system (CNS) and/or leptomeningeal involvement&#xD;
&#xD;
          4. Current peripheral neuropathy ≥ G2&#xD;
&#xD;
          5. Dysphagia or inability to swallow oral medication&#xD;
&#xD;
          6. Malabsorption syndrome or disease significantly affecting GI-function or major&#xD;
             resection of the stomach or proximal small bowel that could affect absorption of oral&#xD;
             vinorelbine&#xD;
&#xD;
          7. Other serious illness or medical condition, such as but not limited to:&#xD;
&#xD;
               -  Clinically significant cardiac disease or impaired cardiac function (such as:&#xD;
                  congestive heart failure requiring treatment (NYHA ≥ II); eft ventricular&#xD;
                  ejection fraction (LVEF) &lt; 50%; significant cardiac arrhythmia; atrial&#xD;
                  fibrillation; conduction abnormality such as congenital long QT syndrome or high&#xD;
                  grade/complete atrioventricular (AV)-blockage; acute coronary syndrome including&#xD;
                  myocardial infarction, unstable angina pectoris, coronary artery bypass graft,&#xD;
                  coronary angioplasty or stenting, if &lt; 3 months prior to registration; QTcF &gt; 480&#xD;
                  msec at screening)&#xD;
&#xD;
               -  Uncontrolled hypertension (&gt; 140/100 mmHg at rest (average of 3 consecutive&#xD;
                  readings))&#xD;
&#xD;
               -  Unstable diabetes mellitus&#xD;
&#xD;
               -  Uncontrolled hypercalcemia&#xD;
&#xD;
               -  Clinically significant active infections (current or within the last 2 weeks&#xD;
                  prior to registration)&#xD;
&#xD;
               -  Previous organ allograft&#xD;
&#xD;
          8. Prior treatment with vinorelbine or other vinca alkaloids&#xD;
&#xD;
          9. Concomitant endocrine therapy (e.g. tamoxifen, aromatase inhibitors, fulvestrant) for&#xD;
             advanced breast cancer&#xD;
&#xD;
         10. Concomitant use of yellow-fever vaccination or other attenuated life vaccine&#xD;
&#xD;
         11. Concomitant treatment with strong CYP3A4-inhibitors or strong CYP3A4-inducers&#xD;
             (discontinuation before registration is acceptable, if medically feasible and&#xD;
             ethically acceptable)&#xD;
&#xD;
         12. Necessity to undergo long-term oxygen therapy&#xD;
&#xD;
         13. Major surgery ≤ 28 days prior to registration and/or no recovery from side effects of&#xD;
             such therapy to baseline condition or ≤ G1&#xD;
&#xD;
         14. Radiotherapy ≤ 28 days prior to registration, no recovery from side effects of such&#xD;
             therapy to baseline condition or ≤ G1 and/or irradiation of ≥ 30% of bone marrow&#xD;
&#xD;
         15. Known hypersensitivity to vinca alkaloids, soy, peanut or any of the excipients&#xD;
             contained in the oral vinorelbine capsules&#xD;
&#xD;
         16. Participation in another clinical trial with any investigational drug ≤ 30 days prior&#xD;
             to registration&#xD;
&#xD;
         17. History of another malignancy within the past 5 years prior to registration, except&#xD;
             cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix&#xD;
&#xD;
         18. Pregnant or nursing (lactating) woman&#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>Marcus Schmidt, Univ.-Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Düsseldorf, Frauenklinik</name>
      <address>
        <city>Dusseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Frankfurt-Höchst Klinik für Gynäkologie und Geburtshilfe - Operative und konservative Gynäkologie, Gynäkologische Onkologie, Pränataldiagnostik, Geburtshilfe</name>
      <address>
        <city>Frankfurt am Main</city>
        <zip>65929</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Gynäkologie</name>
      <address>
        <city>Halle</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onkologische Schwerpunktpraxis Dr. Karcher, Dr. Fuxius, Dr. Debatin</name>
      <address>
        <city>Heidelberg</city>
        <zip>69115</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum des Saarlandes, Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin</name>
      <address>
        <city>Homburg</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der LMU München, Brustzentrum</name>
      <address>
        <city>Munchen</city>
        <zip>80377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Schwerpunktpraxis für Hämatologie und Onkologie Ravensburg</name>
      <address>
        <city>Ravensburg</city>
        <zip>88212</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>August 9, 2019</last_update_submitted>
  <last_update_submitted_qc>August 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Johannes Gutenberg University Mainz</investigator_affiliation>
    <investigator_full_name>Marcus Schmidt, MD</investigator_full_name>
    <investigator_title>Univ.-Prof. Dr. med.</investigator_title>
  </responsible_party>
  <keyword>Breast cancer</keyword>
  <keyword>Vinorelbine</keyword>
  <keyword>Metronomic chemotherapy</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>Vinorelbine</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/NCT03007992
org study id: 2015-007
nct id: NCT03007992
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of the trial is to investigate the efficacy of metronomic treatment with daily
      oral vinorelbine in terms of clinical benefit rate based on local radiological assessment in
      patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy.
In terms of the chronic nature of advanced/metastatic breast cancer, there is a high medical
      need for new treatment options after failure of hormonal treatment that prolong the interval
      to the start of intensive cytotoxic therapy, which is commonly associated with impaired
      quality of life (QoL) and potentially serious side effects. In this respect, metronomic
      treatment with daily administration of oral vinorelbine could provide an efficacious
      treatment option with limited toxicities.

      Accordingly, this national, multi-centre, open-label, single-arm phase II trial aims to
      investigate a truly metronomic schedule with daily oral vinorelbine in HR+/HER2-patients with
      metastatic breast cancer resistant to endocrine therapy, by assessing efficacy and safety.
      Oral vinorelbine will be administered at a daily dose of 30 mg (flat dose without any
      adaptation to body weight or body surface area) without breaks. Treatment will continue until
      disease progression, occurrence of unacceptable toxicity, patient's refusal or investigator's
      decision to stop the treatment.

      In the course of the study, the following interim and final analyses will be done:

      i) 1st interim analysis (safety): This analysis will be performed on the basis of 10
      patients, who were initially included into the study and who are eligible for safety
      evaluation; frequency statistics of (serious) adverse events will be analysed.

      ii) 2nd interim analysis (efficacy): This analysis will be performed at the completion of the
      1st Simon stage.

      iii) Final analysis (complete): This analysis will be performed after completion of the
      follow-up phase (6 months of follow-up after Last Patient Last Treatment).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical Benefit Rate (CBR)
time frame: 24 weeks after start of treatment.
description: The primary endpoint is the determination of the Clinical Benefit Rate (CBR) at 24 weeks after start of treatment. The response to treatment is measured by computer tomography (CT) or magnetic resonance imaging (MRI) for measurable lesions and evaluation for non-measurable lesions at 24 weeks after start of treatment.
measure: Overall response rate (ORR)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Disease control rate (DCR)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Duration of disease control (DoDC)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Duration of stable disease (DoSD)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Duration of response (DoR)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Progression-free survival (PFS)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Time to treatment failure (TTF)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Overall survival (OS)
time frame: 6 months after last patient last treatment
description: Statistical evaluation of above mentioned parameter for each patient measured in duration of month
measure: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 6 months after last patient last treatment
description: Determination of frequency and severity of (serious) adverse events and the number of laboratory values worsening from baseline based on the Common Toxicity Criteria (CTC) Grade; other safety data (e.g. vital signs and special tests) will be considered as appropriate
measure: Patient's symptoms and health-related quality of life
time frame: 6 months after last patient last treatment
description: Evaluation of the Global Health Status/QoL on the basis of the Eastern Cooperative Oncology Group (EORTC) quality of life questionnaire (QLQ)-C30 questionnaire
measure: Histopathological parameters
time frame: before start of treatment and upon progression, assessed up to 6 months after last patient last treatment
description: Analysis of tumour tissue biomarkers before the start of study treatment and upon progression: histopathological analyses including qualitative assessments of tumor-infiltrating lymphocytes (TIL) involving the evaluation of regulatory T cells (Treg), cluster of differentiation 8 (CD8), CD20 and immune checkpoint parameters (e.g. Programmed Death-Ligand 1 (PD-L1)); additionally, markers like vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and hypoxia inducible factor-1 (HIF-1) will be evaluated
measure: Biomarker profiles
time frame: before start of treatment, during treatment period and upon progression, assessed up to 6 months after last patient last treatment
description: Analysis of blood biomarkers before the start of study treatment, during the treatment period and upon progression: assessment of blood biomarkers, such as CD4+ CD25+ Forkhead-Box-Protein P3 (FOXP3+) Treg, T and B lymphocytes, natural killer (NK) cells and monocytes, hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and to evaluate potential correlations of biomarker expression and clinical outcomes (response, PFS, OS)
arm group label: Vinorelbine Oral
arm group type: Experimental
description: Test product: Navelbine® 20 mg / 30 mg soft capsules
intervention type: Drug
intervention name: Vinorelbine
description: Oral vinorelbine will be administered at a daily dose of 30 mg (flat dose without any adaptation to body weight or body surface area) without breaks. Treatment will continue until disease progression, occurrence of unacceptable toxicity, patient's refusal or investigator's decision to stop the treatment.
arm group label: Vinorelbine Oral
other name: Navelbine® soft capsules
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marcus Schmidt, Univ.-Prof. Dr. med.
role: Principal Investigator
affiliation: Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit
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country: Germany
responsible party type: Principal Investigator
investigator affiliation: Johannes Gutenberg University Mainz
investigator full name: Marcus Schmidt, MD
investigator title: Univ.-Prof. Dr. med.
mesh term: Breast Neoplasms
mesh term: Vinorelbine