<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/NCT03820063</url>
  </required_header>
  <id_info>
    <org_study_id>BOOG 2018-01</org_study_id>
    <nct_id>NCT03820063</nct_id>
  </id_info>
  <brief_title>Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study</brief_title>
  <acronym>TRAIN-3</acronym>
  <official_title>Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Borstkanker Onderzoek Groep</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>BOOG Study Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Borstkanker Onderzoek Groep</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided&#xD;
      de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin,&#xD;
      and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      High pathological complete response (pCR)-rates are seen using different neoadjuvant&#xD;
      chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast&#xD;
      cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and&#xD;
      with an even higher rate of &gt;80% in patients with HER2-positive and hormone receptor (HR)&#xD;
      negative tumors. PCR is associated with better long-term outcomes in patients with&#xD;
      HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%.&#xD;
      Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles&#xD;
      of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more&#xD;
      toxicity. Pathological complete responses are sometimes seen after only 10-12 days of&#xD;
      neoadjuvant treatment. It is therefore important to investigate which patients can safely be&#xD;
      treated with less than six cycles of chemotherapy and who requires more than six cycles for&#xD;
      maximum activity.&#xD;
&#xD;
      The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the&#xD;
      pathologic response, although the accuracy differs between breast cancer subtypes. It is&#xD;
      hypothesized that patients with an early complete radiologic response may not benefit from&#xD;
      additional chemotherapy and can be referred for early surgery. Patients who have not achieved&#xD;
      pCR after early surgery despite radiologic complete response (rCR) are candidates for further&#xD;
      adjuvant chemotherapy to complete the initially planned number of treatment cycles and&#xD;
      maintain maximum treatment activity. Imaged guided de-escalation in which the number of&#xD;
      treatment cycles is determined by the radiologic response could thus reduce toxicity in&#xD;
      neoadjuvant treatment while maintaining activity.&#xD;
&#xD;
      This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant&#xD;
      chemotherapy in patients with HER2-positive breast cancer.&#xD;
&#xD;
      To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles&#xD;
      taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.&#xD;
      Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to&#xD;
      complete one full year of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 27, 2019</start_date>
  <completion_date type="Anticipated">May 1, 2032</completion_date>
  <primary_completion_date type="Actual">November 15, 2022</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>
    <intervention_model_description>neoadjuvant courses PTC-Ptz; adjuvant courses Ptz (pCR) or T-DM1 (non-pCR)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event free survival at three years</measure>
    <time_frame>3 years</time_frame>
    <description>Number of patients without progression of disease recurrence, second primary or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival at three years</measure>
    <time_frame>3 years</time_frame>
    <description>Number of patients alive at three years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic complete response in breast and axilla</measure>
    <time_frame>an average of 6 months</time_frame>
    <description>Number of patients with absence of invasive tumor cells in breast and axilla at surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiologic complete response</measure>
    <time_frame>an average of 6 months</time_frame>
    <description>Number of patients with absence of pathologic enhancement on MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of neoadjuvant chemotherapy cycles administered</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>Number of neoadjuvant chemotherapy cycles administered per patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of radical and non-radical resections</measure>
    <time_frame>an average of 6 months</time_frame>
    <description>Number of patients with radical and non-radical resections</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>Number of patients with toxicity grade &gt;= 3 (CTCAE v5.0) until 30 days after last adjuvant administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of cardiotoxicity and neuropathy</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>Number of patients with cardiotoxicity and neuropathy grade &gt;= 2 (CTCAE v5.0) until 30 days after last adjuvant administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of symptomatic LVSD (heart failure),</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>Number of patients with an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease ≥10 percentage points from baseline to a LVEF &lt;50%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grade ≥3 laboratory test abnormalities</measure>
    <time_frame>an average of 1 year</time_frame>
    <description>Number of patients with Grade ≥3 laboratory test abnormalities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of number of tumor positive Vacuum Assisted Core Biopsy</measure>
    <time_frame>an average 6 months</time_frame>
    <description>Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">462</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>PTC-Pz</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8&#xD;
Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1&#xD;
Carboplatin AUC 6mg•ml/min administered intravenously on day 1&#xD;
Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)&#xD;
Treatment cycles are repeated on day 22&#xD;
Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTC-Pz</intervention_name>
    <description>Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8&#xD;
Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1&#xD;
Carboplatin AUC 6mg•ml/min administered intravenously on day 1&#xD;
Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)&#xD;
Treatment cycles are repeated on day 22&#xD;
In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.</description>
    <arm_group_label>PTC-Pz</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed primairy infiltrating breast cancer.&#xD;
&#xD;
          2. Stage II or Ill disease.&#xD;
&#xD;
          3. Overexpression and/or amplification of HER2 in an invasive component of the core&#xD;
             biopsy.&#xD;
&#xD;
          4. Age &lt;:18&#xD;
&#xD;
          5. ECOG Group performance status&#xD;
&#xD;
          6. LVEF &gt;50% measured by echocardiography, MRI or MUGA&#xD;
&#xD;
          7. Known HR-status ( in percentages)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous radiation therapy of chemotherapy&#xD;
&#xD;
          2. Pregnancy or breastfeeding&#xD;
&#xD;
          3. Evidence of distant metastases&#xD;
&#xD;
          4. Evidence of bilateral infiltrating breast cancer&#xD;
&#xD;
          5. Concurrent anti-cancer treatment or another investigational drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>G S Sonke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NKI-AvL</affiliation>
  </overall_official>
  <overall_official>
    <last_name>A E van Leeuwen- Stok, PhD</last_name>
    <role>Study Director</role>
    <affiliation>BOOG Study Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Noordwest Ziekenhuisgroep</name>
      <address>
        <city>Alkmaar</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuisgroep Twente</name>
      <address>
        <city>Almelo</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meander Medisch Centrum</name>
      <address>
        <city>Amersfoort</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Amstelland</name>
      <address>
        <city>Amstelveen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NKI-AVL</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OLVG</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gelre ziekenhuizen</name>
      <address>
        <city>Apeldoorn</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rijnstate</name>
      <address>
        <city>Arnhem</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rode Kruis Ziekenhuis</name>
      <address>
        <city>Beverwijk</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexander Monro ziekenhuis</name>
      <address>
        <city>Bilthoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphia Ziekenhuis</name>
      <address>
        <city>Breda</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reinier de Graaf Groep</name>
      <address>
        <city>Delft</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jeroen Bosch Ziekenhuis</name>
      <address>
        <city>Den Bosch</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haaglanden MC</name>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haga Ziekenhuis</name>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deventer ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>van Weel Bethesda</name>
      <address>
        <city>Dirksland</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nij Smellinghe</name>
      <address>
        <city>Drachten</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuisvoorziening Gelderse Vallei</name>
      <address>
        <city>Ede</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catharina ziekenhuis</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maxima Medisch Centrum</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint Annaziekenhuis</name>
      <address>
        <city>Geldrop</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RIVAS Beatrixziekenhuis</name>
      <address>
        <city>Gorinchem</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groene Hart Ziekenhuis</name>
      <address>
        <city>Gouda</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martini ziekenhuis</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis St. Jansdal</name>
      <address>
        <city>Harderwijk</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tjongerschans</name>
      <address>
        <city>Heerenveen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zuyderland Medisch Centrum</name>
      <address>
        <city>Heerlen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elkerliek ziekenhuis</name>
      <address>
        <city>Helmond</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tergooi</name>
      <address>
        <city>Hilversum</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spaarne Gasthuis</name>
      <address>
        <city>Hoofddorp</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisch Centrum Leeuwarden</name>
      <address>
        <city>Leeuwarden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MUMC</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint Antonius ziekenhuis</name>
      <address>
        <city>Nieuwegein</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canisius Wilhelmina Ziekenhuis</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bernhoven</name>
      <address>
        <city>Oss</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stichting ziekenhuizen West-Friesland en Waterland</name>
      <address>
        <city>Purmerend</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laurentius ziekenhuis</name>
      <address>
        <city>Roermond</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC, Universitair Medisch Centrum Rotterdam</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franciscus Gasthuis en Vlietland</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ikazia Ziekenhuis</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maasstadziekenhuis</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZorgSaam</name>
      <address>
        <city>Terneuzen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rivierenland Ziekenhuis</name>
      <address>
        <city>Tiel</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elisabeth TweeSteden ziekenhuis</name>
      <address>
        <city>Tilburg</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diakonessenhuis Utrecht</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Utrecht</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VieCurie Medisch Centrum voor Noord-Limburg</name>
      <address>
        <city>Venlo</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SKB Ziekenhuis Winterswijk</name>
      <address>
        <city>Winterswijk</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zaans Medisch Centrum</name>
      <address>
        <city>Zaandam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala Klinieken</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 21, 2023</last_update_submitted>
  <last_update_submitted_qc>February 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>neo adjuvant</keyword>
  <keyword>HER2 positive</keyword>
  <keyword>de-escalation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_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/NCT03820063
org study id: BOOG 2018-01
nct id: NCT03820063
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided
      de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin,
      and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.
High pathological complete response (pCR)-rates are seen using different neoadjuvant
      chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast
      cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and
      with an even higher rate of >80% in patients with HER2-positive and hormone receptor (HR)
      negative tumors. PCR is associated with better long-term outcomes in patients with
      HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%.
      Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles
      of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more
      toxicity. Pathological complete responses are sometimes seen after only 10-12 days of
      neoadjuvant treatment. It is therefore important to investigate which patients can safely be
      treated with less than six cycles of chemotherapy and who requires more than six cycles for
      maximum activity.

      The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the
      pathologic response, although the accuracy differs between breast cancer subtypes. It is
      hypothesized that patients with an early complete radiologic response may not benefit from
      additional chemotherapy and can be referred for early surgery. Patients who have not achieved
      pCR after early surgery despite radiologic complete response (rCR) are candidates for further
      adjuvant chemotherapy to complete the initially planned number of treatment cycles and
      maintain maximum treatment activity. Imaged guided de-escalation in which the number of
      treatment cycles is determined by the radiologic response could thus reduce toxicity in
      neoadjuvant treatment while maintaining activity.

      This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant
      chemotherapy in patients with HER2-positive breast cancer.

      To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles
      taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.
      Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to
      complete one full year of treatment.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: neoadjuvant courses PTC-Ptz; adjuvant courses Ptz (pCR) or T-DM1 (non-pCR)
primary purpose: Treatment
masking: None (Open Label)
measure: Event free survival at three years
time frame: 3 years
description: Number of patients without progression of disease recurrence, second primary or death
measure: Overall survival at three years
time frame: 3 years
description: Number of patients alive at three years
measure: Pathologic complete response in breast and axilla
time frame: an average of 6 months
description: Number of patients with absence of invasive tumor cells in breast and axilla at surgery
measure: Radiologic complete response
time frame: an average of 6 months
description: Number of patients with absence of pathologic enhancement on MRI
measure: Number of neoadjuvant chemotherapy cycles administered
time frame: an average of 1 year
description: Number of neoadjuvant chemotherapy cycles administered per patient
measure: Number of radical and non-radical resections
time frame: an average of 6 months
description: Number of patients with radical and non-radical resections
measure: Incidence and severity of adverse events
time frame: an average of 1 year
description: Number of patients with toxicity grade >= 3 (CTCAE v5.0) until 30 days after last adjuvant administration
measure: Incidence and severity of cardiotoxicity and neuropathy
time frame: an average of 1 year
description: Number of patients with cardiotoxicity and neuropathy grade >= 2 (CTCAE v5.0) until 30 days after last adjuvant administration
measure: Incidence of symptomatic LVSD (heart failure),
time frame: an average of 1 year
description: Number of patients with an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease ≥10 percentage points from baseline to a LVEF <50%
measure: Grade ≥3 laboratory test abnormalities
time frame: an average of 1 year
description: Number of patients with Grade ≥3 laboratory test abnormalities
measure: Incidence of number of tumor positive Vacuum Assisted Core Biopsy
time frame: an average 6 months
description: Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI
arm group label: PTC-Pz
arm group type: Experimental
description: Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8
Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1
Carboplatin AUC 6mg•ml/min administered intravenously on day 1
Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)
Treatment cycles are repeated on day 22
Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.
intervention type: Drug
intervention name: PTC-Pz
description: Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8
Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1
Carboplatin AUC 6mg•ml/min administered intravenously on day 1
Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)
Treatment cycles are repeated on day 22
In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.
arm group label: PTC-Pz
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: G S Sonke, MD
role: Principal Investigator
affiliation: NKI-AvL
last name: A E van Leeuwen- Stok, PhD
role: Study Director
affiliation: BOOG Study Center
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country: Netherlands
responsible party type: Sponsor
mesh term: Breast Neoplasms