<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/NCT03272477</url>
  </required_header>
  <id_info>
    <org_study_id>PH002-TP-II</org_study_id>
    <nct_id>NCT03272477</nct_id>
  </id_info>
  <brief_title>Study to Compare Neoadjuvant Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy and Quality of Life Assessment Under Adjuvant Therapy in Operable HER2+/HR+ Breast Cancer Patients</brief_title>
  <acronym>TP-II</acronym>
  <official_title>A Prospective, Randomized, Multicenter, Open-label Comparison of Pre-surgical Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy Given for Twelve Weeks With a Quality of Life Assessment of Trastuzumab, Pertuzumab in Combination With Standard (Neo)Adjuvant Treatment in Patients With Operable HER2+/HR+ Breast Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Palleos Healthcare GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>WSG WOMEN´S HEALTHCARE STUDY GROUP</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cankado GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Palleos Healthcare GmbH</source>
  <oversight_info>
    <has_dmc>Yes</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 prospective, phase IIa, multicenter, randomized, open-label study comparing a&#xD;
      pre-surgical combination of trastuzumab and pertuzumab with concurrent weekly paclitaxel&#xD;
      chemotherapy or endocrine therapy given for 12 weeks with a quality of life assessment for 40&#xD;
      additional weeks in patients with operable HER2+/HR+ breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 5, 2017</start_date>
  <completion_date type="Anticipated">February 28, 2024</completion_date>
  <primary_completion_date type="Actual">July 14, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological complete response (pCR)</measure>
    <time_frame>14 weeks after start of therapy treatment</time_frame>
    <description>14 weeks after start of therapy treatment, tumor and lymph node biopsy is performed to reach the primary endpoint of pathological complete response (pCR) which is defined as the absence of residual invasive cancer of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/is ypN0 in the current AJCC staging system). As secondary endpoint, also other response states will be taken into account: no invasive tumor in the complete resected breast specimen irrespective of the lymph node state following completion of neoadjuvant systemic therapy (ypT0/is, any ypN).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life using EORTC QBL-BR-23 scale</measure>
    <time_frame>During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first</time_frame>
    <description>Assessment of quality of life questions during the past week or during the past 4 weeks (depending on the questions) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life using EQ5D-5L scale</measure>
    <time_frame>During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first</time_frame>
    <description>questions about &quot;self care&quot;, &quot;usual activities&quot;, &quot;pain /discomfort&quot;, anxiety/depression&quot; are assessed on a 5 level-scale using tick boxes : &quot;I have no problem&quot;; &quot;I have slight problems&quot;; &quot;I have moderate problems&quot;; &quot;I have severe problems&quot; &quot;I am unable&quot;&#xD;
assessment of the patient health (good or bad) is measured on a scale numbered from 0 to 100 (100 means the best heath and 0 means the worst)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life using EORTC QLQ-C30 scale</measure>
    <time_frame>During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first</time_frame>
    <description>Assessment of quality of life questions (activities, breath, pain, sleep, appetite, vomiting, constipation, others..) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)&#xD;
Assessment of Overall health and overall quality of life during the past week is measured on a 7 level-scale going from 1 (very poor) to 7 (excellent)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor size reduction by mammography</measure>
    <time_frame>at screening visit and 12 weeks after start of therapy treatment</time_frame>
    <description>The diameters of the tumors in the breast will be measured in millimeter by mammography as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor size reduction by palpation and ultrasound</measure>
    <time_frame>at screening visit and 4, 7 and 13 weeks after start of therapy treatment</time_frame>
    <description>The diameters of the tumors in the breast will be measured in millimeter by palpation and ultrasound as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 60 months</time_frame>
    <description>The overall survival is defined as time (days) between study treatment allocation and death of patient due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of invasive disease-free survival</measure>
    <time_frame>From date of treatment allocation until the date of first documented progression or secondary tumor or date of death from any cause, whichever came first, assessed up to 60 months (study duration including follow up)</time_frame>
    <description>Duration of invasive disease-free survival is defined as time (days) between study treatment allocation and relapse, secondary tumor event or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of mastectomies</measure>
    <time_frame>14 weeks after start of therapy treatment</time_frame>
    <description>The number of mastectomies will be determined at time of surgery (week 14 and week 18)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ki67 level</measure>
    <time_frame>4 weeks after start of therapy treatment</time_frame>
    <description>The level of Ki67 in biopsie material will be measured at week 4 of neoadjuvant therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cDNA composition</measure>
    <time_frame>at baseline, 3 weeks, 4 weeks and 6, 18, 24, 36 48 and 60 months after start of therapy treatment</time_frame>
    <description>The composition of cDNA in blood samples will be measured</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">257</enrollment>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.&#xD;
Adjuvant Therapy: Standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.&#xD;
Adjuvant Therapy: Standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perjeta Injectable Product</intervention_name>
    <description>Single dose of 840mg (loading dose) day1 cycle 1, 420mg at day1 of each subsequent cycle, every 3 weeks. (The latter cycle is called cycle of treatment and is to be given 4 times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
    <other_name>Pertuzumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Herceptin</intervention_name>
    <description>Single dose of 8mg/kg (loading dose) day1 cycle 1; 6mg/kg at day1 of each subsequent cycle body weight every 3 weeks. (This is called cycle of treatment and is to be given four times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
    <other_name>Trastuzumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen</intervention_name>
    <description>20 mg per day for a total of 40 weeks in the adjuvant therapy phase.</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>80mg/sqm, day one of each cycle, every week. This is called a cycle of treatment and is to be given for 12 weeks in neoadjuvant therapy phase.</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>12 weeks (4cycles) of max. 90mg/sqm in adjuvant therapy phase</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>12 weeks (4cycles) of 600 mg/sqm i.v. on day 1+8 or 12 weeks (4cycles) of 500 mg/sqm i.v. on day 1 in adjuvant therapy phase</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole</intervention_name>
    <description>1mg per day for a total of 40 weeks in adjuvant therapy phase</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>2,5 mg/day for a total of 40 weeks in adjuvant therapy phase</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane</intervention_name>
    <description>25mg/day for a total of 40 weeks in adjuvant therapy phase</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leuprorelin acetate</intervention_name>
    <description>One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin</intervention_name>
    <description>3,6mg every 28 days or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.</description>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole</intervention_name>
    <description>1mg per day for 12 weeks in neoadjuvant therapy phase; 1mg per day for a total of 40 weeks max. in adjuvant therapy phase</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>2,5 mg per day for 12 weeks in neoadjuvant therapy phase; 2,5 mg perday for a total of 40 weeks max. in adjuvant therapy phase</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane</intervention_name>
    <description>25mg/day for 12 weeks in neoadjuvant therapy phase; 25mg/day for a total of 40 weeks max. in adjuvant therapy phase</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>80mg/sqm, day one of each cycle, every week. This is called a cycle of treatment an is to be given for 12 weeks in the adjuvant phase</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen</intervention_name>
    <description>20mg per day (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase.</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leuporelin acetate</intervention_name>
    <description>One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase).</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin</intervention_name>
    <description>3,5mg every 28 days or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase).</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Core biopsy at screening (outside of protocol), at week 4 after randomization, (at week 14 in addition if neoadjuvant phase is prolonged)</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery</intervention_name>
    <description>Surgery at week 14 after randomization (or later, if neoadjuvant phase is prolonged)</description>
    <arm_group_label>Endocrine+Trastuzumab+Pertuzumab</arm_group_label>
    <arm_group_label>Paclitaxel+Trastuzumab+Pertuzumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female patients, age at diagnosis 18 years and older&#xD;
&#xD;
          -  Histologically confirmed unilateral primary invasive carcinoma of the breast&#xD;
&#xD;
          -  Patients must qualify for neoadjuvant treatment as follows:&#xD;
&#xD;
               -  No clinical evidence for distant metastasis (M0)&#xD;
&#xD;
               -  Clinical cT1c-T4a-c (participation of patients with tumors &gt; cT2 is strongly&#xD;
                  recommended) and no evidence for distant metastases (M0)&#xD;
&#xD;
               -  All clinical N (participation of patients with cN+, also in case of cT1c, is&#xD;
                  strongly recommended)&#xD;
&#xD;
               -  Known positive HR-status and centrally confirmed HER2+-status by IHC/FISH&#xD;
&#xD;
               -  Patients need to fulfill adequate blood count and organ function to receive&#xD;
                  chemotherapy (see exclusion criteria).&#xD;
&#xD;
          -  Tumor block available for central pathology review&#xD;
&#xD;
          -  Performance Status ECOG ≤ 1 or KI ≥ 80%&#xD;
&#xD;
          -  Negative pregnancy test (urine or serum) within 7 days prior to registration in&#xD;
             premenopausal patients&#xD;
&#xD;
          -  Patients of childbearing potential must accept to implement a highly effective (less&#xD;
             than 1% failure rate according to Pearl index) non-hormonal contraceptive measures&#xD;
             during the study treatment and for 6 months following the last dose of study treatment&#xD;
             (trastuzumab and pertuzumab) such as:&#xD;
&#xD;
               -  Intrauterine device (IUD)&#xD;
&#xD;
               -  bilateral tubal occlusion&#xD;
&#xD;
               -  vasectomised partner&#xD;
&#xD;
               -  sexual abstinence&#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;
          -  LVEF &gt; 55%; LVEF within normal limits of each institution measured by echocardiography&#xD;
             (within 42 days prior to randomization)&#xD;
&#xD;
          -  Normal ECG (within 42 days prior to randomization)&#xD;
&#xD;
        Exclusion Criteria:&#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&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs and participation in another&#xD;
             clinical trial or clinical research project within 30 days prior to study entry is&#xD;
             excluded&#xD;
&#xD;
          -  Male breast cancer&#xD;
&#xD;
          -  Concurrent pregnancy&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Sequential breast cancer&#xD;
&#xD;
          -  Reasons indicating risk of poor compliance&#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 including but not confined to:&#xD;
&#xD;
               -  Uncompensated chronic heart failure or systolic dysfunction (LVEF &lt; 55%, CHF NYHA&#xD;
                  classes II-IV),&#xD;
&#xD;
               -  unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart&#xD;
                  rate ≥ 100/min at rest, significant ventricular arrhythmia (ventricular&#xD;
                  tachycardia) or higher-grade AV-block,&#xD;
&#xD;
               -  Angina pectoris within the last 6 months requiring anti-anginal medication,&#xD;
&#xD;
               -  Clinically significant valvular heart disease,&#xD;
&#xD;
               -  Evidence of myocardial infarction on electrocardiogram (ECG),&#xD;
&#xD;
               -  Poorly controlled hypertension (e.g., systolic &gt; 180 mm Hg or diastolic &gt; 100 mm&#xD;
                  Hg).&#xD;
&#xD;
          -  Inadequate organ function including but not confined to:&#xD;
&#xD;
               -  hepatic impairment (Child Pugh Class C)&#xD;
&#xD;
               -  pulmonary disease (severe dyspnea at rest requiring oxygen therapy)&#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>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Iris Reiser, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Palleos Healthcare GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Evangelisches Krankenhaus Bethesda Mönchengladbach</name>
      <address>
        <city>Mönchengladbach</city>
        <zip>41061</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. doi: 10.1200/JCO.2015.62.1268. Epub 2015 Nov 2.</citation>
    <PMID>26527775</PMID>
  </reference>
  <reference>
    <citation>Vaz-Luis I, Ottesen RA, Hughes ME, Marcom PK, Moy B, Rugo HS, Theriault RL, Wilson J, Niland JC, Weeks JC, Lin NU. Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study. Breast Cancer Res. 2012 Oct 1;14(5):R129. doi: 10.1186/bcr3324.</citation>
    <PMID>23025714</PMID>
  </reference>
  <reference>
    <citation>Prat A, Cheang MC, Galvan P, Nuciforo P, Pare L, Adamo B, Munoz M, Viladot M, Press MF, Gagnon R, Ellis C, Johnston S. Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib. JAMA Oncol. 2016 Oct 1;2(10):1287-1294. doi: 10.1001/jamaoncol.2016.0922.</citation>
    <PMID>27281556</PMID>
  </reference>
  <reference>
    <citation>Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SKL, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-377. doi: 10.1016/S1470-2045(15)00551-3. Epub 2016 Feb 10.</citation>
    <PMID>26874901</PMID>
  </reference>
  <reference>
    <citation>Loibl S, von Minckwitz G, Blohmer J, et al: pCR as a Surrogate in HER2-Positive Patients Treated with Trastuzumab. Supplement to Cancer Research 71:[S5-4] 2011</citation>
  </reference>
  <reference>
    <citation>Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41. doi: 10.1056/NEJMoa1406281. Erratum In: N Engl J Med. 2015 Nov 12;373(20):1989.</citation>
    <PMID>25564897</PMID>
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  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>October 4, 2022</last_update_submitted>
  <last_update_submitted_qc>October 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hormone receptor positive</keyword>
  <keyword>human epidermal growth factor receptor 2 positive</keyword>
  <keyword>Early breast cancer</keyword>
  <keyword>HR+/HER2+</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>Tamoxifen</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Pertuzumab</mesh_term>
    <mesh_term>Anastrozole</mesh_term>
    <mesh_term>Exemestane</mesh_term>
    <mesh_term>Goserelin</mesh_term>
    <mesh_term>Leuprolide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03272477
org study id: PH002-TP-II
nct id: NCT03272477
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, phase IIa, multicenter, randomized, open-label study comparing a
      pre-surgical combination of trastuzumab and pertuzumab with concurrent weekly paclitaxel
      chemotherapy or endocrine therapy given for 12 weeks with a quality of life assessment for 40
      additional weeks in patients with operable HER2+/HR+ breast cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological complete response (pCR)
time frame: 14 weeks after start of therapy treatment
description: 14 weeks after start of therapy treatment, tumor and lymph node biopsy is performed to reach the primary endpoint of pathological complete response (pCR) which is defined as the absence of residual invasive cancer of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/is ypN0 in the current AJCC staging system). As secondary endpoint, also other response states will be taken into account: no invasive tumor in the complete resected breast specimen irrespective of the lymph node state following completion of neoadjuvant systemic therapy (ypT0/is, any ypN).
measure: Health-related quality of life using EORTC QBL-BR-23 scale
time frame: During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first
description: Assessment of quality of life questions during the past week or during the past 4 weeks (depending on the questions) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
measure: Health-related quality of life using EQ5D-5L scale
time frame: During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first
description: questions about "self care", "usual activities", "pain /discomfort", anxiety/depression" are assessed on a 5 level-scale using tick boxes : "I have no problem"; "I have slight problems"; "I have moderate problems"; "I have severe problems" "I am unable"
assessment of the patient health (good or bad) is measured on a scale numbered from 0 to 100 (100 means the best heath and 0 means the worst)
measure: Health-related quality of life using EORTC QLQ-C30 scale
time frame: During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first
description: Assessment of quality of life questions (activities, breath, pain, sleep, appetite, vomiting, constipation, others..) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
Assessment of Overall health and overall quality of life during the past week is measured on a 7 level-scale going from 1 (very poor) to 7 (excellent)
measure: Tumor size reduction by mammography
time frame: at screening visit and 12 weeks after start of therapy treatment
description: The diameters of the tumors in the breast will be measured in millimeter by mammography as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
measure: Tumor size reduction by palpation and ultrasound
time frame: at screening visit and 4, 7 and 13 weeks after start of therapy treatment
description: The diameters of the tumors in the breast will be measured in millimeter by palpation and ultrasound as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
measure: Overall survival
time frame: From date of randomization until the date of death from any cause, assessed up to 60 months
description: The overall survival is defined as time (days) between study treatment allocation and death of patient due to any cause.
measure: Duration of invasive disease-free survival
time frame: From date of treatment allocation until the date of first documented progression or secondary tumor or date of death from any cause, whichever came first, assessed up to 60 months (study duration including follow up)
description: Duration of invasive disease-free survival is defined as time (days) between study treatment allocation and relapse, secondary tumor event or death.
measure: Number of mastectomies
time frame: 14 weeks after start of therapy treatment
description: The number of mastectomies will be determined at time of surgery (week 14 and week 18)
measure: Ki67 level
time frame: 4 weeks after start of therapy treatment
description: The level of Ki67 in biopsie material will be measured at week 4 of neoadjuvant therapy
measure: cDNA composition
time frame: at baseline, 3 weeks, 4 weeks and 6, 18, 24, 36 48 and 60 months after start of therapy treatment
description: The composition of cDNA in blood samples will be measured
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
arm group type: Active Comparator
description: Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group type: Experimental
description: Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
intervention type: Drug
intervention name: Perjeta Injectable Product
description: Single dose of 840mg (loading dose) day1 cycle 1, 420mg at day1 of each subsequent cycle, every 3 weeks. (The latter cycle is called cycle of treatment and is to be given 4 times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
other name: Pertuzumab
intervention type: Drug
intervention name: Herceptin
description: Single dose of 8mg/kg (loading dose) day1 cycle 1; 6mg/kg at day1 of each subsequent cycle body weight every 3 weeks. (This is called cycle of treatment and is to be given four times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
other name: Trastuzumab
intervention type: Drug
intervention name: Tamoxifen
description: 20 mg per day for a total of 40 weeks in the adjuvant therapy phase.
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Paclitaxel
description: 80mg/sqm, day one of each cycle, every week. This is called a cycle of treatment and is to be given for 12 weeks in neoadjuvant therapy phase.
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Epirubicin
description: 12 weeks (4cycles) of max. 90mg/sqm in adjuvant therapy phase
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Cyclophosphamide
description: 12 weeks (4cycles) of 600 mg/sqm i.v. on day 1+8 or 12 weeks (4cycles) of 500 mg/sqm i.v. on day 1 in adjuvant therapy phase
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Anastrozole
description: 1mg per day for a total of 40 weeks in adjuvant therapy phase
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Letrozole
description: 2,5 mg/day for a total of 40 weeks in adjuvant therapy phase
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Exemestane
description: 25mg/day for a total of 40 weeks in adjuvant therapy phase
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Leuprorelin acetate
description: One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Goserelin
description: 3,6mg every 28 days or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Anastrozole
description: 1mg per day for 12 weeks in neoadjuvant therapy phase; 1mg per day for a total of 40 weeks max. in adjuvant therapy phase
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Letrozole
description: 2,5 mg per day for 12 weeks in neoadjuvant therapy phase; 2,5 mg perday for a total of 40 weeks max. in adjuvant therapy phase
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Exemestane
description: 25mg/day for 12 weeks in neoadjuvant therapy phase; 25mg/day for a total of 40 weeks max. in adjuvant therapy phase
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Paclitaxel
description: 80mg/sqm, day one of each cycle, every week. This is called a cycle of treatment an is to be given for 12 weeks in the adjuvant phase
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Tamoxifen
description: 20mg per day (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase.
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Leuporelin acetate
description: One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase).
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Drug
intervention name: Goserelin
description: 3,5mg every 28 days or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase).
arm group label: Endocrine+Trastuzumab+Pertuzumab
intervention type: Diagnostic Test
intervention name: Biopsy
description: Core biopsy at screening (outside of protocol), at week 4 after randomization, (at week 14 in addition if neoadjuvant phase is prolonged)
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
intervention type: Procedure
intervention name: Surgery
description: Surgery at week 14 after randomization (or later, if neoadjuvant phase is prolonged)
arm group label: Endocrine+Trastuzumab+Pertuzumab
arm group label: Paclitaxel+Trastuzumab+Pertuzumab
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Iris Reiser, PhD
role: Study Director
affiliation: Palleos Healthcare GmbH
facility: 
country: Germany
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responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Tamoxifen
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Cyclophosphamide
mesh term: Trastuzumab
mesh term: Letrozole
mesh term: Epirubicin
mesh term: Pertuzumab
mesh term: Anastrozole
mesh term: Exemestane
mesh term: Goserelin
mesh term: Leuprolide
sharing ipd: No