<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/NCT02214381</url>
  </required_header>
  <id_info>
    <org_study_id>WSG-AM06 / ADAPT Elderly</org_study_id>
    <nct_id>NCT02214381</nct_id>
  </id_info>
  <brief_title>A Prospective, Multicenter, Open-label 12 Week Neoadjuvant Phase II Trial Optimizing Taxane Therapy in Elderly Patients With Low Response</brief_title>
  <official_title>A Prospective, Multicenter, Open-label Comparison of Pre-surgical Myocet/ Cyclophosphamide (MC) q3w Followed by Either MC or Paclitaxel - Depending on Early Response Assessment by Ultrasound or by Toxicity for Elderly Non Frail Primary Breast Cancer Patients With Increased Risk of Relapse.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>West German Study Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Teva Pharmaceuticals USA</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>West German Study Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Comparison of pre-surgical Myocet/ Cyclophosphamide (MC) q3w followed by either MC or&#xD;
      Paclitaxel - depending on early response assessment by ultrasound or by toxicity for elderly&#xD;
      non frail primary breast cancer patients with increased risk of relapse.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 3</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>Comparison of pCR rates in patients with early response and no severe toxicity (Group 1) and in other patients (Group 2).</measure>
    <time_frame>After 5 years of follow-up.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of febrile neutropenia (FN) after 1 x MC in patients with primary prophylaxis (PP) vs. others.</measure>
    <time_frame>After 5 years of follow-up.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity in the 4 x MC versus 2 x MC followed 6 x Pac arm as measured by adverse events.</measure>
    <time_frame>After 5 years of follow-up.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of pCR in non-responders to MC.</measure>
    <time_frame>After 5 years of follow-up.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>G-CSF use in terms of primary or secondary prophylaxis per patient including occurence febrile neutropenia per patient per cycle</measure>
    <time_frame>After 5 years of follow-up.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Early Primary Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Mycet/Cyclophosphamid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4 x Myocet 60 mg/m² q3w in combination with 4 x cyclophosphamide 600 mg/m² q3w depending on early response assessment by ultrasound or on toxicity profile.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Myocet/Cyclophosphamide/Paclitaxel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 x Myocet 60 mg/m² q3w in combination with 2 x cyclophosphamide 600 mg/m² q3w followed by 6 x paclitaxel 80 mg/m² q1w depending on early response assessment by ultrasound or on toxicity profile.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Myocet</intervention_name>
    <arm_group_label>Mycet/Cyclophosphamid</arm_group_label>
    <arm_group_label>Myocet/Cyclophosphamide/Paclitaxel</arm_group_label>
    <other_name>Doxorubicin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <arm_group_label>Mycet/Cyclophosphamid</arm_group_label>
    <arm_group_label>Myocet/Cyclophosphamide/Paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <arm_group_label>Myocet/Cyclophosphamide/Paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General Inclusion Criteria for ADAPT:&#xD;
&#xD;
          -  Female patients, age at diagnosis 18 years and above (consider patients at 70 years&#xD;
             and above for ADAPT Elderly)&#xD;
&#xD;
          -  Candidate for chemotherapy on the basis of conventional criteria&#xD;
&#xD;
          -  Histologically confirmed unilateral primary invasive carcinoma of the breast&#xD;
&#xD;
          -  Clinical T1 - T4a-c&#xD;
&#xD;
          -  All clinical N (cN)&#xD;
&#xD;
          -  No clinical evidence for distant metastasis (M0)&#xD;
&#xD;
          -  Known HR status and HER2 status (local pathology)&#xD;
&#xD;
          -  Tumor block available for central pathology review&#xD;
&#xD;
          -  Performance Status ECOG &lt;= 1 or KI &gt;= 80%&#xD;
&#xD;
          -  Written informed consent prior to beginning specific protocol procedures, including&#xD;
             expected cooperation of the patients for the treatment and follow-up, must be obtained&#xD;
             and documented according to the local regulatory requirements&#xD;
&#xD;
          -  The patient must be accessible for treatment and follow-up&#xD;
&#xD;
          -  Patients must qualify for neoadjuvant treatment&#xD;
&#xD;
          -  LVEF &gt; 50%; LVEF within normal limits of each institution measured by echocardiography&#xD;
             and normal ECG (within 42 days prior to chemotherapy)&#xD;
&#xD;
               -  Laboratory requirements :&#xD;
&#xD;
                    -  Leucocytes ≥ 3.5 x 109/L&#xD;
&#xD;
                    -  Platelets ≥ 100 x 109/L&#xD;
&#xD;
                    -  Hemoglobin ≥ 10 g/dL&#xD;
&#xD;
                    -  Total bilirubin ≤ 1 x ULN&#xD;
&#xD;
                    -  ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x UNL&#xD;
&#xD;
                    -  Creatinine ≤ 175 µmol/L (2 mg/dl)&#xD;
&#xD;
        Additional inclusion criteria ADAPT Elderly:&#xD;
&#xD;
          -  ≥ 70 years old&#xD;
&#xD;
          -  Charlson scale ≤ 2&#xD;
&#xD;
          -  HR+/HER2- disease: if RS and sequential testing are available N0-1/RS 12-25/poor&#xD;
             response or N0-1/RS ≥26&#xD;
&#xD;
          -  All G3 with Ki-67 ≥40% in tumors &gt;1cm&#xD;
&#xD;
          -  All N2&#xD;
&#xD;
          -  All TN&#xD;
&#xD;
          -  All subtypes&#xD;
&#xD;
        General Exclusion Criteria for ADAPT:&#xD;
&#xD;
          -  Known hypersensitivity reaction to the compounds or incorporated substances&#xD;
&#xD;
          -  Prior malignancy with a disease-free survival of &lt; 10 years, except curatively treated&#xD;
             basalioma of the skin, pTis of the cervix uteri&#xD;
&#xD;
          -  Non-operable breast cancer including inflammatory breast cancer&#xD;
&#xD;
          -  Previous or concurrent treatment with cytotoxic agents for any reason after&#xD;
             consultation with the sponsor&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs. Participation in another clinical&#xD;
             trial with any investigational not marketed drug within 30 days prior to study entry&#xD;
             (concurrent participation in non-interventional post authorization safety studies not&#xD;
             influencing the primary study endpoints is allowed, e.g. WSG PROTROCA for evaluation&#xD;
             of primary/secondary G-CSF prophylaxis)&#xD;
&#xD;
          -  Male breast cancer&#xD;
&#xD;
          -  Sequential breast cancer&#xD;
&#xD;
          -  Reasons indicating risk of poor compliance&#xD;
&#xD;
          -  Patient not able to consent&#xD;
&#xD;
        Additional Exclusion Criteria ADAPT Elderly:&#xD;
&#xD;
          -  Known polyneuropathy ≥ grade 2&#xD;
&#xD;
          -  Severe and relevant co-morbidity that would interact with the application of cytotoxic&#xD;
             agents or the participation in the study&#xD;
&#xD;
          -  Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.)&#xD;
&#xD;
          -  Uncompensated cardiac function (current unstable ventricular arrhythmia requiring&#xD;
             treatment, history of symptomatic CHF NYHA classes II-IV), history of myocardial&#xD;
             infarction or unstable angina pectoris within 12 months of enrollment, history of&#xD;
             severe hypertension, CAD - coronary artery disease)&#xD;
&#xD;
          -  Severe dyspnea&#xD;
&#xD;
          -  Pneumonitis&#xD;
&#xD;
          -  Abnormal blood values:&#xD;
&#xD;
          -  Thrombocytopenia &gt; CTCAE grade 1&#xD;
&#xD;
          -  Increases in ALT/AST &gt; CTCAE grade 1&#xD;
&#xD;
          -  Hypokalaemia &gt; CTCAE grade 1&#xD;
&#xD;
          -  Neutropenia &gt; CTCAE grade 1&#xD;
&#xD;
          -  Anaemia &gt; CTCAE grade 1&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nadia Harbeck, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern, Munich, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ulrike Nitz, Prof. Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ev. Krankenhaus Bethesda Brustzentrum Niederrhein</name>
      <address>
        <city>Moenchengladbach</city>
        <zip>41061</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern</name>
      <address>
        <city>Munich</city>
        <zip>81337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <last_update_submitted>March 23, 2023</last_update_submitted>
  <last_update_submitted_qc>March 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>breast cancer</keyword>
  <keyword>elderly</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>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</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/NCT02214381
org study id: WSG-AM06 / ADAPT Elderly
nct id: NCT02214381
lead sponsor: 
collaborator: 
has dmc: Yes
Comparison of pre-surgical Myocet/ Cyclophosphamide (MC) q3w followed by either MC or
      Paclitaxel - depending on early response assessment by ultrasound or by toxicity for elderly
      non frail primary breast cancer patients with increased risk of relapse.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Comparison of pCR rates in patients with early response and no severe toxicity (Group 1) and in other patients (Group 2).
time frame: After 5 years of follow-up.
measure: Incidence of febrile neutropenia (FN) after 1 x MC in patients with primary prophylaxis (PP) vs. others.
time frame: After 5 years of follow-up.
measure: Toxicity in the 4 x MC versus 2 x MC followed 6 x Pac arm as measured by adverse events.
time frame: After 5 years of follow-up.
measure: Number of pCR in non-responders to MC.
time frame: After 5 years of follow-up.
measure: G-CSF use in terms of primary or secondary prophylaxis per patient including occurence febrile neutropenia per patient per cycle
time frame: After 5 years of follow-up.
arm group label: Mycet/Cyclophosphamid
arm group type: Active Comparator
description: 4 x Myocet 60 mg/m² q3w in combination with 4 x cyclophosphamide 600 mg/m² q3w depending on early response assessment by ultrasound or on toxicity profile.
arm group label: Myocet/Cyclophosphamide/Paclitaxel
arm group type: Active Comparator
description: 2 x Myocet 60 mg/m² q3w in combination with 2 x cyclophosphamide 600 mg/m² q3w followed by 6 x paclitaxel 80 mg/m² q1w depending on early response assessment by ultrasound or on toxicity profile.
intervention type: Drug
intervention name: Myocet
arm group label: Mycet/Cyclophosphamid
arm group label: Myocet/Cyclophosphamide/Paclitaxel
other name: Doxorubicin
intervention type: Drug
intervention name: Cyclophosphamide
arm group label: Mycet/Cyclophosphamid
arm group label: Myocet/Cyclophosphamide/Paclitaxel
intervention type: Drug
intervention name: Paclitaxel
arm group label: Myocet/Cyclophosphamide/Paclitaxel
criteria: 
gender: Female
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Nadia Harbeck, Prof. Dr.
role: Principal Investigator
affiliation: Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern, Munich, Germany
last name: Ulrike Nitz, Prof. Dr.
role: Study Chair
affiliation: Ev. Krankenhaus Bethesda Brustzentrum Niederrhein, Mönchengladbach, Germany
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Doxorubicin