<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/NCT01690325</url>
  </required_header>
  <id_info>
    <org_study_id>WSG-AM05</org_study_id>
    <nct_id>NCT01690325</nct_id>
  </id_info>
  <brief_title>Imaging for Response Assessment of Neoadjuvant Chemotherapy in Primary Breast Cancer (GALADON)</brief_title>
  <official_title>Molecular Imaging for Response Assessment of Bevacizumab + Docetaxel as Neoadjuvant Chemotherapy in Primary Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>West German Study Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>West German Study Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The GALADON trial is a diagnostic and interventional study in which different molecular&#xD;
      imaging methods as Positon Emission Tomography (PET), different kind of Magnetic Resonance&#xD;
      Imaging - methods (MRI, DWI and DCE-MRI) will be compared with common imaging methods&#xD;
      (mammography, ultrasound) to see if there can detect an early response to a combined&#xD;
      neoadjuvant therapy with bevacizumab and docetaxel in patients with locally advanced breast&#xD;
      cancer. Neoadjuvant chemotherapy (this means patients were treated before the tumor was&#xD;
      removed by surgery) with a drug like trastuzumab (monoclonal antibody) which is target to the&#xD;
      Her2-protein is much more powerful than with chemotherapy alone because it is normalizing the&#xD;
      blood supply and improves tumor delivery of conventional chemotherapy like docetaxel. The&#xD;
      HER2 protein is only available in about 30 % of breast cancer types. bevacizumab is another&#xD;
      humanized monoclonal antibody like trastuzumab but is effective not only in patients with an&#xD;
      positive HER2 status and in combination with trastuzumab it may emphasize the effect in&#xD;
      reduction of tumor growth. Bevacizumab is approved in advanced disease, but no major&#xD;
      neoadjuvant data available so far for primary breast cancer. As the therapy with monoclonal&#xD;
      antibody regimes are expensive and may cause severe side effects predictive factors to select&#xD;
      patients who will benefit from such highly specific drugs before therapy start would be&#xD;
      medically and economically highly valuable. In this study the efficacy of combined&#xD;
      neoadjuvant chemotherapy with bevacizumab, trastuzumab and docetaxel in Arm A and bevacizumab&#xD;
      and docetaxel in Arm B should be evaluated and the predictive impact of different imaging&#xD;
      methods for tumor response should be shown.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Therapy of HER2+ patients according to protocol was no longer appropriate. Patient enrolment&#xD;
    behind planned schedule and challenges of site performance&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of pathological complete response (pCR) following neoadjuvant therapy in group A and group B</measure>
    <time_frame>about 18 weeks (start of neoadjuvant chemotherapy until surgery)</time_frame>
    <description>To determine efficacy of cytotoxic-antiangiogenic neoadjuvant therapy in primary breast cancer: bevacizumab+trastuzumab+docetaxel fro group A (HER2 positive) or bevacizumab+docetaxel for group B (HER2 negative) using pathological complete response (pCR) as the primary endpoint.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm A: Neoadjuvant: 6 cycles of Docetaxel every 21 days together with 6 cycles of Avastin and Herceptin; Adjuvant: 4 cycles of Epirubicin and Cyclophosphamid every 21 days together with 12 cycles of Herceptin every 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm B: neoadjuvant: 6 cycles of Docetaxel and Avastin every 21 days. Adjuvant: 4 cycles of Epirubicin and Cyclophosphamid every 21 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <arm_group_label>Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.</arm_group_label>
    <arm_group_label>Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <arm_group_label>Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <arm_group_label>Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.</arm_group_label>
    <arm_group_label>Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <arm_group_label>Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.</arm_group_label>
    <arm_group_label>Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamid</intervention_name>
    <arm_group_label>Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.</arm_group_label>
    <arm_group_label>Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Arm A / Arm B&#xD;
&#xD;
          -  Age ≥ 18 years and ≤ 65 years&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Operable, locally advanced primary breast cancer (≥ cT2, N0 or N+, M0) histologically&#xD;
             confirmed by core biopsy&#xD;
&#xD;
          -  Histologically confirmed unilateral, solitaire breast cancer&#xD;
&#xD;
          -  Patients who are candidates for neoadjuvant chemotherapy according to AGO guidelines&#xD;
             (www.ago-online.de) with unifocal lesion&#xD;
&#xD;
          -  HER2 positive disease (IHC 3+ and/or FISH positive)or&#xD;
&#xD;
          -  HER2 negative disease (IHC 0/1+, IHC 2+ and/or FISH negative)&#xD;
&#xD;
          -  Baseline LVEF ≥ 55% (measured by MUGA or echocardiography) according to institution&#xD;
             specific norm&#xD;
&#xD;
          -  Informed consent for clinical trial including analysis of predictive imaging tests and&#xD;
             biomarkers&#xD;
&#xD;
          -  Clinically or by imaging (mammogram, MRI or US) assessed breast cancer ≥ 2 cm or&#xD;
             inflammatory breast cancer with bi-dimensional measurable lesion independent of nodal&#xD;
             status&#xD;
&#xD;
          -  Negative pregnancy test (urine or serum) within 7 days prior to registration if&#xD;
             patient is premenopausal with intact reproductive organs and if patient is less than&#xD;
             one year after menopause&#xD;
&#xD;
          -  ECOG Performance status 0-2&#xD;
&#xD;
          -  Adequate organ function for cytotoxic chemotherapy&#xD;
&#xD;
          -  Adequate renal function including Serum creatinine ≤ ULN, Measured or calculated&#xD;
             creatinine clearance &gt; 60 ml/min&#xD;
&#xD;
          -  Urine dipstick for proteinuria &lt; 2+. In case of ≥ 2+ proteinuria on dipstick&#xD;
             urinalysis, a 24-hour urine collection must be performed and protein per 24 hours must&#xD;
             be ≤ 1.0 g&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1500 cells/μl, platelet count ≥ 100,000 cells/μl&#xD;
&#xD;
          -  Bilirubin ≤ ULN; ALT or AST ≤ 1.5 x ULN, and alkaline phosphatase &lt; 2.5 x ULN&#xD;
&#xD;
          -  Patients must be available and compliant for treatment and follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Arm A / Arm B&#xD;
&#xD;
          -  Evidence of distant metastases by clinical or imaging diagnosis&#xD;
&#xD;
          -  Multifocal primary tumour, defined as histologically confirmed tumour-manifestations&#xD;
             within different quadrants; distance ≥ 4 cm&#xD;
&#xD;
          -  Pre-existing motor or sensory neuropathy of a severity ≥ grade 2 NCI criteria&#xD;
&#xD;
          -  Previous breast cancer&#xD;
&#xD;
          -  Prior malignancy with a disease-free survival of &lt; 5 years&#xD;
&#xD;
          -  Prior malignancy which has not been curatively treated&#xD;
&#xD;
          -  Inflammatory breast cancer without bi-dimensional measurable lesion&#xD;
&#xD;
          -  Prior systemic therapy for cancer&#xD;
&#xD;
          -  Previous therapy with trastuzumab or other anti-HER2 agent (for HER2+ tumors)&#xD;
&#xD;
          -  Previous therapy with bevacizumab or other anti-VEGF agent&#xD;
&#xD;
          -  Patients with immunosuppressive therapy&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Women of childbearing potential not using highly effective birth control.&#xD;
&#xD;
          -  Patients with known hypersensitivity reactions to the compounds or incorporated&#xD;
             substances of trastuzumab or its constituents (for HER2+ tumors).&#xD;
&#xD;
          -  Patients with known hypersensitivity reactions to the compounds or incorporated&#xD;
             substances of bevacizumab or its constituents.&#xD;
&#xD;
          -  Invasive malignancy which could affect compliance with the protocol or interpretation&#xD;
             of results.&#xD;
&#xD;
          -  Other serious illness or medical condition including:&#xD;
&#xD;
               -  Known or suspected congestive heart failure (&gt;NYHA I) and/or coronary heart&#xD;
                  disease&#xD;
&#xD;
               -  Angina pectoris requiring antianginal medication&#xD;
&#xD;
               -  Previous history of myocardial infarction&#xD;
&#xD;
               -  Evidence of transmural infarction on ECG&#xD;
&#xD;
               -  Un- or poorly controlled arterial hypertension (i.e. BP &gt;150/100 mmHg under&#xD;
                  treatment with two antihypertensive drugs)&#xD;
&#xD;
               -  Rhythm abnormalities requiring permanent treatment&#xD;
&#xD;
               -  Clinically significant valvular heart disease&#xD;
&#xD;
               -  Patients with dyspnoea at rest due to malignant or other disease or who require&#xD;
                  supportive oxygen therapy&#xD;
&#xD;
               -  Active serious uncontrolled infections&#xD;
&#xD;
               -  Poorly controlled diabetes&#xD;
&#xD;
               -  History of hypertensive crisis or hypertensive encephalopathy&#xD;
&#xD;
               -  History of TIA or CVA&#xD;
&#xD;
               -  History of any arterial thrombotic event within 12 months before randomization&#xD;
&#xD;
          -  Inadequate bone marrow, hepatic and renal functions as evidenced by the following:&#xD;
&#xD;
          -  Neutrophil count of &lt; 1500, platelet count of &lt; 100,000/µL&#xD;
&#xD;
          -  Haemoglobin &lt; 10 g/dL&#xD;
&#xD;
          -  Serum total bilirubin &gt; ULN (except for patients with clearly documented Gilbert's&#xD;
             syndrome)&#xD;
&#xD;
          -  ALT or AST &gt; 1.5 x ULN&#xD;
&#xD;
          -  Alkaline phosphatase &gt; 2.5 x ULN, serum creatinine &gt; ULN&#xD;
&#xD;
          -  Concurrent treatment with any other anti-cancer therapy&#xD;
&#xD;
          -  No informed consent for analysis of predictive imaging tests and biomarkers&#xD;
&#xD;
          -  Contraindications against MRI: Cardiac pacemakers, other forms of medical or&#xD;
             biostimulation implants, ferromagnetic foreign bodies or metallic implants (e.g.&#xD;
             surgical protheses, aneurysm clips), implanted insulin pumps, valvular implants,&#xD;
             allergy to contrast agent, renal insufficiency, claustrophobia&#xD;
&#xD;
          -  Active peptic ulcer, incomplete wound healing or unhealed bone fracture&#xD;
&#xD;
          -  Previous thromboembolic events, known hemorrhagic diathesis, coagulopathy with&#xD;
             increased bleeding risk, or treatment with anticoagulants. Current or recent (within&#xD;
             10 days of first dose of bevacizumab) use of acetalic acid (&gt; 325 mg/day) or&#xD;
             clopidogrel (&gt; 75 mg/day)&#xD;
&#xD;
          -  Disease significantly affecting gastrointestinal function, e.g. malabsorption&#xD;
             syndrome, resection of the stomach or small bowel, ulcerative colitis; abdominal&#xD;
             fistula, intra-abdominal abscess within 6 months of enrolment or gastrointestinal&#xD;
             perforation&#xD;
&#xD;
          -  Major surgery within the last 28 days or anticipation of the need for major surgery&#xD;
             during study treatment with bevacizumab. No minor surgeries including insertion of an&#xD;
             indwelling catheter within 24h prior to registration.&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs; participation in another clinical&#xD;
             trial with any investigational drug within 30 days prior to study entry&#xD;
&#xD;
          -  Chronic daily treatment with corticosteroids (dose of &gt; 10 mg/day methylprednisolone&#xD;
             equivalent) (excluding inhaled steroids).&#xD;
&#xD;
          -  Patients with a history of hypersensitivity reaction to docetaxel or to drugs&#xD;
             formulated with polysorbate 80&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nadia Harbeck, Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Head of Breast Centre, University of Munich, Grosshadern Hospital, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Breast Centre, University of Munich, LMU</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 18, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>August 9, 2018</last_update_submitted>
  <last_update_submitted_qc>August 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <keyword>Neoadjuvant cytotoxic-antiangiogenic therapy</keyword>
  <keyword>Bevacizumab</keyword>
  <keyword>PET</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>Cyclophosphamide</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Epirubicin</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/NCT01690325
org study id: WSG-AM05
nct id: NCT01690325
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The GALADON trial is a diagnostic and interventional study in which different molecular
      imaging methods as Positon Emission Tomography (PET), different kind of Magnetic Resonance
      Imaging - methods (MRI, DWI and DCE-MRI) will be compared with common imaging methods
      (mammography, ultrasound) to see if there can detect an early response to a combined
      neoadjuvant therapy with bevacizumab and docetaxel in patients with locally advanced breast
      cancer. Neoadjuvant chemotherapy (this means patients were treated before the tumor was
      removed by surgery) with a drug like trastuzumab (monoclonal antibody) which is target to the
      Her2-protein is much more powerful than with chemotherapy alone because it is normalizing the
      blood supply and improves tumor delivery of conventional chemotherapy like docetaxel. The
      HER2 protein is only available in about 30 % of breast cancer types. bevacizumab is another
      humanized monoclonal antibody like trastuzumab but is effective not only in patients with an
      positive HER2 status and in combination with trastuzumab it may emphasize the effect in
      reduction of tumor growth. Bevacizumab is approved in advanced disease, but no major
      neoadjuvant data available so far for primary breast cancer. As the therapy with monoclonal
      antibody regimes are expensive and may cause severe side effects predictive factors to select
      patients who will benefit from such highly specific drugs before therapy start would be
      medically and economically highly valuable. In this study the efficacy of combined
      neoadjuvant chemotherapy with bevacizumab, trastuzumab and docetaxel in Arm A and bevacizumab
      and docetaxel in Arm B should be evaluated and the predictive impact of different imaging
      methods for tumor response should be shown.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of pathological complete response (pCR) following neoadjuvant therapy in group A and group B
time frame: about 18 weeks (start of neoadjuvant chemotherapy until surgery)
description: To determine efficacy of cytotoxic-antiangiogenic neoadjuvant therapy in primary breast cancer: bevacizumab+trastuzumab+docetaxel fro group A (HER2 positive) or bevacizumab+docetaxel for group B (HER2 negative) using pathological complete response (pCR) as the primary endpoint.
arm group label: Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.
arm group type: Experimental
description: Arm A: Neoadjuvant: 6 cycles of Docetaxel every 21 days together with 6 cycles of Avastin and Herceptin; Adjuvant: 4 cycles of Epirubicin and Cyclophosphamid every 21 days together with 12 cycles of Herceptin every 21 days.
arm group label: Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid
arm group type: Experimental
description: Arm B: neoadjuvant: 6 cycles of Docetaxel and Avastin every 21 days. Adjuvant: 4 cycles of Epirubicin and Cyclophosphamid every 21 days.
intervention type: Drug
intervention name: Docetaxel
arm group label: Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.
arm group label: Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid
intervention type: Drug
intervention name: Trastuzumab
arm group label: Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.
other name: Herceptin
intervention type: Drug
intervention name: Bevacizumab
arm group label: Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.
arm group label: Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid
other name: Avastin
intervention type: Drug
intervention name: Epirubicin
arm group label: Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.
arm group label: Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid
intervention type: Drug
intervention name: Cyclophosphamid
arm group label: Docetaxel, Avastin, Herceptin; adjuv. Epirubicin, Cyclophos.
arm group label: Docetaxel, Avastin; adjuvant Epirubicin, Cyclophosphamid
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Nadia Harbeck, Prof. Dr. med.
role: Principal Investigator
affiliation: Head of Breast Centre, University of Munich, Grosshadern Hospital, Germany
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Cyclophosphamide
mesh term: Bevacizumab
mesh term: Docetaxel
mesh term: Trastuzumab
mesh term: Epirubicin