<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/NCT02187744</url>
  </required_header>
  <id_info>
    <org_study_id>B3271004</org_study_id>
    <secondary_id>REFLECTIONS B327-04</secondary_id>
    <secondary_id>2013-004679-11</secondary_id>
    <secondary_id>REFLECTIONS (B327-04)</secondary_id>
    <nct_id>NCT02187744</nct_id>
  </id_info>
  <brief_title>A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)</brief_title>
  <official_title>A RANDOMIZED, DOUBLE-BLIND PHARMACOKINETIC STUDY OF PF-05280014 PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN VERSUS HERCEPTIN (REGISTERED) PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN FOR THE NEOADJUVANT TREATMENT OF PATIENTS WITH OPERABLE HER2-POSITIVE BREAST CANCER</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014&#xD;
      (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus&#xD;
      Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin&#xD;
      (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant&#xD;
      setting. The hypothesis to be tested in this study is the percentage of patients with steady&#xD;
      state Cycle 5 Ctrough (Cycle 6 pre-dose) &gt;20 µg/mL of trastuzumab-Pfizer is similar to&#xD;
      EU-approved trastuzumab, using a margin of -12.5%.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2014</start_date>
  <completion_date type="Actual">March 9, 2016</completion_date>
  <primary_completion_date type="Actual">March 9, 2016</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) &gt;20 µg/mL at Cycle 5.</measure>
    <time_frame>Cycle 5</time_frame>
    <description>The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) &gt;20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.</measure>
    <time_frame>Cycles 1 through 6</time_frame>
    <description>Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.</measure>
    <time_frame>Cycle 6/End of treatment</time_frame>
    <description>Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.</measure>
    <time_frame>Cycle 6/End of treatment</time_frame>
    <description>ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.</measure>
    <time_frame>Cycles 1 through 6</time_frame>
    <description>The number of participants with positive (titer &gt;=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.</measure>
    <time_frame>Cycles 1 through 6</time_frame>
    <description>The number of participants with positive (NAb response &gt;=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">226</enrollment>
  <condition>Early Breast Cancer</condition>
  <arm_group>
    <arm_group_label>PF-05280014</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Herceptin®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PF-05280014</intervention_name>
    <description>Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.</description>
    <arm_group_label>PF-05280014</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Taxotere®</intervention_name>
    <description>Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.</description>
    <arm_group_label>PF-05280014</arm_group_label>
    <other_name>docetaxel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paraplatin®</intervention_name>
    <description>Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.</description>
    <arm_group_label>PF-05280014</arm_group_label>
    <other_name>carboplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Trastuzumab-EU</intervention_name>
    <description>Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.</description>
    <arm_group_label>Herceptin®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Taxotere®</intervention_name>
    <description>Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.</description>
    <arm_group_label>Herceptin®</arm_group_label>
    <other_name>docetaxel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paraplatin®</intervention_name>
    <description>Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.</description>
    <arm_group_label>Herceptin®</arm_group_label>
    <other_name>carboplatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed HER2 overexpressing invasive breast cancer.&#xD;
&#xD;
          -  Plan for definitive surgical resection of breast tumor (i.e., lumpectomy or&#xD;
             mastectomy, and sentinel node (SN) biopsy or axillary lymph node dissection (ALND).&#xD;
&#xD;
          -  Plan for neoadjuvant chemotherapy.&#xD;
&#xD;
          -  Measurable disease in the breast after diagnostic biopsy, defined as longest diameter&#xD;
             ≥ 2.0 cm.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bilateral breast cancer.&#xD;
&#xD;
          -  Inflammatory breast cancer.&#xD;
&#xD;
          -  Presence of known distant metastases.&#xD;
&#xD;
          -  Received prior treatment, including chemotherapy, endocrine therapy, biologic therapy,&#xD;
             radiation or surgery with the exception of diagnostic biopsy for primary breast&#xD;
             cancer.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Compassionate Cancer Care Medical Group, Inc.</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Oncology (Imaging Facility)</name>
      <address>
        <city>Kingwood</city>
        <state>Texas</state>
        <zip>77339</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Oncology (Imaging Facility)</name>
      <address>
        <city>Shenandoah</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Oncology</name>
      <address>
        <city>Shenandoah</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI 'Republican Research and Practice Centre of Oncology and Medical Radiology n.a. N.N. Alexandrov'</name>
      <address>
        <city>Lesnoy</city>
        <state>Minsk Region</state>
        <zip>223040</zip>
        <country>Belarus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Hradec Kralove</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bacs-Kiskun Megyei Korhaz</name>
      <address>
        <city>Kecskemet</city>
        <state>Bacs-kiskun</state>
        <zip>6000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem Altalanos Orvostudomanyi Kar-I. sz. Belgyogyaszati Klinika Onkologiai Reszleg</name>
      <address>
        <city>Budapest</city>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szent Imre Egyetemi Oktato Korhaz</name>
      <address>
        <city>Budapest</city>
        <zip>1115</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uzsoki Utcai Korhaz, Onkoradiologia, Sugarterapia Fovarosi Onkoradiologiai Kozpont</name>
      <address>
        <city>Budapest</city>
        <zip>1145</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktatokorhaz,</name>
      <address>
        <city>Miskolc</city>
        <zip>3526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet</name>
      <address>
        <city>Szolnok</city>
        <zip>5000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Division of Medical Senology</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Divisione di Oncologia Medica B</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Nazionale Tumori Regina Elena (IRE)</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dept. of Surgery</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpitale Wojewodzkie w Gdyni Sp. z o.o., Oddzial Onkoligii i Radioterapii</name>
      <address>
        <city>Gdynia</city>
        <zip>81-519</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oddzial Chorob Rozrostowych</name>
      <address>
        <city>Lodz</city>
        <zip>93-513</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie</name>
      <address>
        <city>Olsztyn</city>
        <zip>10-228</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Healthcare Institution &quot;Leningrad Regional Oncological Dispensary&quot;</name>
      <address>
        <city>Kuzmolovo</city>
        <state>Leningrad Region</state>
        <zip>188663</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;State Budgetary Healthcare Institution &quot;&quot;Republican Clinical Oncological Dispensary of the Ministry</name>
      <address>
        <city>Ufa</city>
        <state>Republic Bashkortost</state>
        <zip>450054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Budgetary Healthcare Institution &quot;Kursk regional clinical oncological Dispensary&quot;</name>
      <address>
        <city>Kislino Settlement</city>
        <state>Ryshkovskiy Village Council</state>
        <zip>305524</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;State Budgetary Healthcare Institution of Stavropol Region &quot;&quot;Pyatigorsk Oncological Dispensary&quot;&quot;&quot;</name>
      <address>
        <city>Pyatigorsk</city>
        <state>Stavropol Region</state>
        <zip>357502</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Healthcare Institution &quot;Volgograd Regional Oncological Dispensary #3&quot;</name>
      <address>
        <city>Volzhskiy</city>
        <state>Volgograd Region</state>
        <zip>404130</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBHI &quot;Regional Oncology Dispensary&quot;</name>
      <address>
        <city>Irkutsk</city>
        <zip>664035</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Budgetary Healthcare Institution</name>
      <address>
        <city>Kursk</city>
        <zip>305035</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBI &quot;Russian Oncology Scientific center n.a. N. N. Blokhin&quot; RAMS</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Institution Of Healthcare</name>
      <address>
        <city>Moscow</city>
        <zip>129301</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBHI of NNR &quot;Clinical diagnostic center&quot;</name>
      <address>
        <city>Nizhniy Novgorod</city>
        <zip>603006</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Healthcare Institution of NNR &quot;Nizhniy Novgorod Regional Oncological Dispensary&quot;</name>
      <address>
        <city>Nizhniy Novgorod</city>
        <zip>603081</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Budgetary Institution of healthcare of Omsk region &quot;Clinical oncological dispensary&quot;</name>
      <address>
        <city>Omsk</city>
        <zip>644046</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Educational Institution of Higher Professional Education &quot;North-Western State</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>195067</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Peterbsurg Clinical Oncological dispensary of Moscow district</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>196247</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State Budgetary Healthcare Institution &quot;Oncological Dispensary of Moscow District&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>196247</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC RAMSAY Diagnostic RUS</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197046</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Federal State Institution &quot;&quot;Scientific Research Institute of Oncology n.a. N.N.Petrov&quot;&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State Budgetary Institution of healthcare &quot;City Clinical Oncological Dispensary&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>198255</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SRBHI &quot;Regional Clinical Oncology Dispensary&quot;</name>
      <address>
        <city>Velikiy Novgorod</city>
        <zip>173023</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute For Oncology And Radiology Of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onkologicky ustav sv. Alzbety, s.r.o.</name>
      <address>
        <city>Bratislava</city>
        <zip>812 50</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodny Onkologicky ustav</name>
      <address>
        <city>Bratislava</city>
        <zip>833 10</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vychodoslovensky onkologicky ustav, a.s.</name>
      <address>
        <city>Kosice</city>
        <zip>04191</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Healthcare Institution 'Chernihiv Regional Oncology Dispensary', Mamology Department</name>
      <address>
        <city>Chernihiv</city>
        <zip>14029</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MI 'City Dnipropetrovsk Multi-field Clin. Hospital #4 of DRC', Dep.-nt of Chemotherapy;</name>
      <address>
        <city>Dnipropetrovsk</city>
        <zip>49102</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI &quot;Institute of Medical Radiology n.a.S.P. Hrygoriev of National Academy</name>
      <address>
        <city>Kharkiv</city>
        <zip>61024</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Munincipal Healthcare Institution&quot;Kharkiv Regional Clinical Oncologic Center</name>
      <address>
        <city>Kharkiv</city>
        <zip>61070</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Khmelnytskyi Regional Oncologic Dispensary</name>
      <address>
        <city>Khmelnytskyi</city>
        <zip>29009</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MI 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'</name>
      <address>
        <city>Kryvyi Rih</city>
        <zip>50048</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lviv State Oncologic Regional Treatment and Diagnostic Center</name>
      <address>
        <city>Lviv</city>
        <zip>79031</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Institution 'Odesa Regional Clinical Hospital', Mamology Center</name>
      <address>
        <city>Odesa</city>
        <zip>65025</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Municipal Institution &quot;Sumy Regional Clinical Oncology Dispensary&quot;, Thoracic Department</name>
      <address>
        <city>Sumy</city>
        <zip>40005</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vinnytsia Regional Oncology Clinical Dispensary, Chemotherapy Department</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21029</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belarus</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Slovakia</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3271004&amp;StudyName=A%20Randomized%2C%20Double-blind%20Pharmacokinetic%20Study%20Of%20Pf-05280014%20Plus%20Taxotere%20%28registered%29%20And%20Carboplatin%20Versus%20Herceptin%20%28registered%29%20Plus%20Taxotere%20%28registered%29%20And%20Carboplatin%20For%20The%20Neoadjuvant%20Treatment%20Of%20Patients%20With%20Operable%20Her2-positive%20Breast%20Cancer</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <results_first_submitted>February 22, 2017</results_first_submitted>
  <results_first_submitted_qc>February 22, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 7, 2017</results_first_posted>
  <last_update_submitted>December 19, 2018</last_update_submitted>
  <last_update_submitted_qc>December 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Biosimilars</keyword>
  <keyword>Non-inferiority</keyword>
  <keyword>Neoadjuvant Setting</keyword>
  <keyword>Early Breast Cancer</keyword>
  <keyword>PK</keyword>
  <keyword>Phase 3</keyword>
  <keyword>Trastuzumab</keyword>
  <keyword>Herceptin</keyword>
  <keyword>HER2 Positive</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>Carboplatin</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
    <ipd_url>https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A single participant was randomized but not treated; this participant was included in the ITT population, but not in the Participant Flow, Per Protocol, or Safety populations.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>PF-05280014</title>
          <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle.</description>
        </group>
        <group group_id="P2">
          <title>Trastuzumab-EU</title>
          <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="113">Received treatment</participants>
                <participants group_id="P2" count="112">Received treatment</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="109"/>
                <participants group_id="P2" count="106"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participant refused further follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Related adverse event, not serious</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Related adverse event, serious non-fatal</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Treatment</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="113"/>
                <participants group_id="P2" count="112"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="109"/>
                <participants group_id="P2" count="107"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Related adverse event, serious non-fatal</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Related adverse event, not serious</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant refused continued treatment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who were randomized into the study.</population>
      <group_list>
        <group group_id="B1">
          <title>PF-05280014</title>
          <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
        </group>
        <group group_id="B2">
          <title>Trastuzumab-EU</title>
          <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="114"/>
            <count group_id="B2" value="112"/>
            <count group_id="B3" value="226"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.0" spread="11.9"/>
                    <measurement group_id="B2" value="51.2" spread="12.7"/>
                    <measurement group_id="B3" value="52.6" spread="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="114"/>
                    <measurement group_id="B2" value="112"/>
                    <measurement group_id="B3" value="226"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) &gt;20 µg/mL at Cycle 5.</title>
        <description>The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) &gt;20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.</description>
        <time_frame>Cycle 5</time_frame>
        <population>All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-05280014</title>
            <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Trastuzumab-EU</title>
            <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) &gt;20 µg/mL at Cycle 5.</title>
          <description>The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) &gt;20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.</description>
          <population>All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.1" lower_limit="85.0" upper_limit="96.5"/>
                    <measurement group_id="O2" value="93.3" lower_limit="85.9" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The hypothesis to be tested in this study is the percentage of participants with steady state (Cycle 5) Ctrough &gt;20 μg/mL of PF-05280014 is non-inferior to trastuzumab-EU using a margin of -12.5%.</non_inferiority_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.76</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.70</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.02</ci_lower_limit>
            <ci_upper_limit>6.49</ci_upper_limit>
            <estimate_desc>Stratified analysis was based on the normal approximation to the binomial distribution, adjusting for the randomization strata of primary tumor size, estrogen receptor status and by progesterone receptor status.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The hypothesis to be tested in this study is the percentage of participants with steady state (Cycle 5) Ctrough &gt;20 μg/mL of PF-05280014 is non-inferior to trastuzumab-EU using a margin of -12.5%.</non_inferiority_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.18</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.78</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.59</ci_lower_limit>
            <ci_upper_limit>6.23</ci_upper_limit>
            <estimate_desc>Unstratified analysis.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.</title>
        <description>Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.</description>
        <time_frame>Cycles 1 through 6</time_frame>
        <population>All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-05280014</title>
            <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Trastuzumab-EU</title>
            <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.</title>
          <description>Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.</description>
          <population>All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
          <units>μg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1/Day 1 0 hours N= 101, 88</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.313" spread="17.949"/>
                    <measurement group_id="O2" value="1.318" spread="12.366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1/Day 1 1 hour N= 97, 80</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="160.4" spread="57.329"/>
                    <measurement group_id="O2" value="164.8" spread="47.033"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2/Day 21 0 hours N= 99, 88</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.29" spread="13.796"/>
                    <measurement group_id="O2" value="27.20" spread="10.650"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4/Day 63 0 hours N= 98, 89</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.43" spread="14.488"/>
                    <measurement group_id="O2" value="37.33" spread="15.629"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5/Day 84 0 hours N= 101, 87</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.01" spread="15.571"/>
                    <measurement group_id="O2" value="40.44" spread="26.765"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 5/Day 84 1 hour N= 90, 80</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="137.0" spread="37.748"/>
                    <measurement group_id="O2" value="138.8" spread="37.417"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6/Day 105 0 hours N= 101, 89</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.77" spread="17.523"/>
                    <measurement group_id="O2" value="40.10" spread="16.670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.</title>
        <description>Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.</description>
        <time_frame>Cycle 6/End of treatment</time_frame>
        <population>All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-05280014</title>
            <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Trastuzumab-EU</title>
            <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.</title>
          <description>Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.</description>
          <population>All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="86"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" lower_limit="36.9" upper_limit="57.2"/>
                    <measurement group_id="O2" value="50.0" lower_limit="39.0" upper_limit="61.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.81</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.03</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.58</ci_lower_limit>
            <ci_upper_limit>10.96</ci_upper_limit>
            <estimate_desc>Stratified analysis was based on the normal approximation to the binomial distribution, adjusting for the randomization strata of primary tumor size, estrogen receptor status and by progesterone receptor status.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-3.00</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.35</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.40</ci_lower_limit>
            <ci_upper_limit>11.40</ci_upper_limit>
            <estimate_desc>Unstratified analysis.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.</title>
        <description>ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.</description>
        <time_frame>Cycle 6/End of treatment</time_frame>
        <population>All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-05280014</title>
            <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Trastuzumab-EU</title>
            <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.</title>
          <description>ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.</description>
          <population>All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.1" lower_limit="80.2" upper_limit="93.7"/>
                    <measurement group_id="O2" value="82.0" lower_limit="72.5" upper_limit="89.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>5.96</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.09</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.01</ci_lower_limit>
            <ci_upper_limit>15.94</ci_upper_limit>
            <estimate_desc>Stratified analysis was based on the normal approximation to the binomial distribution, adjusting for the randomization strata of primary tumor size, estrogen receptor status and by progesterone receptor status.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>6.10</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.19</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.08</ci_lower_limit>
            <ci_upper_limit>16.27</ci_upper_limit>
            <estimate_desc>Unstratified analysis.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.</title>
        <description>The number of participants with positive (titer &gt;=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.</description>
        <time_frame>Cycles 1 through 6</time_frame>
        <population>All participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-05280014</title>
            <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Trastuzumab-EU</title>
            <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.</title>
          <description>The number of participants with positive (titer &gt;=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.</description>
          <population>All participants who received at least 1 dose of study drug.</population>
          <units>Number of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 (n=113,112)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 (n=111,112)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 (n=108,109)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6 (n=108,108)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.</title>
        <description>The number of participants with positive (NAb response &gt;=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.</description>
        <time_frame>Cycles 1 through 6</time_frame>
        <population>All participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>PF-05280014</title>
            <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
          <group group_id="O2">
            <title>Trastuzumab-EU</title>
            <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.</title>
          <description>The number of participants with positive (NAb response &gt;=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.</description>
          <population>All participants who received at least 1 dose of study drug.</population>
          <units>Number of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="113"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 (n=113,112)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 (n=110,112)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 (n=108,110)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6 (n=108,108)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose.</time_frame>
      <desc>Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.</desc>
      <group_list>
        <group group_id="E1">
          <title>PF-05280014</title>
          <description>Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
        </group>
        <group group_id="E2">
          <title>Trastuzumab-EU</title>
          <description>Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA, version 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Gastrointestinal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Injection site abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA, version 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="106" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="106" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="51" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="112"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="72" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="69" subjects_at_risk="112"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Pfizer CT.gov Call Center</name_or_title>
      <organization>Pfizer, Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02187744
org study id: B3271004
secondary id: REFLECTIONS B327-04
secondary id: 2013-004679-11
secondary id: REFLECTIONS (B327-04)
nct id: NCT02187744
lead sponsor: 
has dmc: Yes
The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014
      (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus
      Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin
      (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant
      setting. The hypothesis to be tested in this study is the percentage of patients with steady
      state Cycle 5 Ctrough (Cycle 6 pre-dose) >20 µg/mL of trastuzumab-Pfizer is similar to
      EU-approved trastuzumab, using a margin of -12.5%.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.
time frame: Cycle 5
description: The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) >20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.
measure: Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.
time frame: Cycles 1 through 6
description: Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.
measure: Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.
time frame: Cycle 6/End of treatment
description: Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.
measure: Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.
time frame: Cycle 6/End of treatment
description: ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.
measure: Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.
time frame: Cycles 1 through 6
description: The number of participants with positive (titer >=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.
measure: Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.
time frame: Cycles 1 through 6
description: The number of participants with positive (NAb response >=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.
arm group label: PF-05280014
arm group type: Experimental
arm group label: Herceptin®
arm group type: Active Comparator
intervention type: Biological
intervention name: PF-05280014
description: Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.
arm group label: PF-05280014
intervention type: Drug
intervention name: Taxotere®
description: Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
arm group label: PF-05280014
other name: docetaxel
intervention type: Drug
intervention name: Paraplatin®
description: Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
arm group label: PF-05280014
other name: carboplatin
intervention type: Biological
intervention name: Trastuzumab-EU
description: Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.
arm group label: Herceptin®
intervention type: Drug
intervention name: Taxotere®
description: Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
arm group label: Herceptin®
other name: docetaxel
intervention type: Drug
intervention name: Paraplatin®
description: Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
arm group label: Herceptin®
other name: carboplatin
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
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country: Belarus
country: Czechia
country: Hungary
country: Italy
country: Poland
country: Russian Federation
country: Serbia
country: Slovakia
country: Ukraine
country: United States
country: Czech Republic
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3271004&StudyName=A%20Randomized%2C%20Double-blind%20Pharmacokinetic%20Study%20Of%20Pf-05280014%20Plus%20Taxotere%20%28registered%29%20And%20Carboplatin%20Versus%20Herceptin%20%28registered%29%20Plus%20Taxotere%20%28registered%29%20And%20Carboplatin%20For%20The%20Neoadjuvant%20Treatment%20Of%20Patients%20With%20Operable%20Her2-positive%20Breast%20Cancer
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Carboplatin
mesh term: Docetaxel
mesh term: Trastuzumab
sharing ipd: Yes
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
ipd url: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.
point of contact: 