<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/NCT03036488</url>
  </required_header>
  <id_info>
    <org_study_id>3475-522</org_study_id>
    <secondary_id>173567</secondary_id>
    <secondary_id>MK-3475-522</secondary_id>
    <secondary_id>KEYNOTE-522</secondary_id>
    <secondary_id>2016-004740-11</secondary_id>
    <nct_id>NCT03036488</nct_id>
  </id_info>
  <brief_title>Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)</brief_title>
  <official_title>A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475)&#xD;
      plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs&#xD;
      placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC).&#xD;
&#xD;
      After a screening phase of approximately 28 days, each participant will receive neoadjuvant&#xD;
      study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the&#xD;
      randomization schedule for approximately 24 weeks (8 cycles). Each participant will then&#xD;
      undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant&#xD;
      study treatment. After definitive surgery, each participant will receive adjuvant study&#xD;
      treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following&#xD;
      adjuvant study treatment, each participant will be monitored for safety, survival and disease&#xD;
      recurrence.&#xD;
&#xD;
      The primary study hypothesis is that pembrolizumab is superior to placebo, in combination&#xD;
      with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or&#xD;
      Event-free Survival (EFS), in participants with locally advanced TNBC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 7, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2025</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>Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery</measure>
    <time_frame>Up to approximately 27-30 weeks</time_frame>
    <description>pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free Survival (EFS) as assessed by Investigator</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pCR rate using an alternative definition, ypT0 ypN0 (i.e., no invasive or noninvasive residual in breast or nodes) at the time of definitive surgery</measure>
    <time_frame>Up to approximately 27-30 weeks</time_frame>
    <description>pCR rate (ypT0 ypN0) is defined as the percentage of participants without residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing Programmed Death-Ligand 1 (PD-L1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery</measure>
    <time_frame>Up to approximately 27-30 weeks</time_frame>
    <description>pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in participants with tumors expressing PD-L1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EFS in participants with tumors expressing PD-L1</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery</measure>
    <time_frame>Up to approximately 27-30 weeks</time_frame>
    <description>pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing PD-L1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis will be censored at the date of the last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who experience an adverse event (AE)</measure>
    <time_frame>Up to approximately 61 weeks</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who discontinue study treatment due to an AE</measure>
    <time_frame>Up to approximately 57 weeks</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score</measure>
    <time_frame>Up to approximately 27-30 weeks</time_frame>
    <description>The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-C30 score will be presented for all participants and for participants with tumors expressing PD-L1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) score</measure>
    <time_frame>Up to approximately 27-30 weeks</time_frame>
    <description>The EORTC-QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life of breast cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-BR23 score will be presented for all participants and for participants with tumors expressing PD-L1.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1174</enrollment>
  <condition>Triple Negative Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receive placebo (normal saline solution) Q3W + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by placebo + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of placebo Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; intravenous (IV) infusion.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>On Day 1 of Cycles 1-4 of the neoadjuvant phase of the study OR on Days 1, 8, 15 of Cycles 1-4 of the neoadjuvant phase of the study; IV infusion.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <other_name>PARAPLATIN®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <other_name>TAXOL®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <other_name>ADRIAMYCIN®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <other_name>ELLENCE®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <other_name>CYTOXAN®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>normal saline solution or dextrose: On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; IV infusion</description>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim</intervention_name>
    <description>For prevention of neutropenia, filgrastim 5 μg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgastrim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.</description>
    <arm_group_label>Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Placebo + Chemotherapy</arm_group_label>
    <other_name>NEUPOGEN®</other_name>
    <other_name>NEULASTA®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the&#xD;
             most recent American Society of Clinical Oncology (ASCO)/College of American&#xD;
             Pathologists (CAP) guidelines.&#xD;
&#xD;
          -  Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the&#xD;
             following combined primary tumor (T) and regional lymph node (N) staging per current&#xD;
             American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as&#xD;
             assessed by the investigator based on radiological and/or clinical assessment:&#xD;
&#xD;
               -  T1c, N1-N2&#xD;
&#xD;
               -  T2, N0-N2&#xD;
&#xD;
               -  T3, N0-N2&#xD;
&#xD;
               -  T4a-d, N0-N2&#xD;
&#xD;
          -  Provides a core needle biopsy consisting of at least 2 separate tumor cores from the&#xD;
             primary tumor at screening to the central laboratory.&#xD;
&#xD;
          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed&#xD;
             within 10 days of treatment initiation.&#xD;
&#xD;
          -  Demonstrates adequate organ function.&#xD;
&#xD;
          -  Males and female participants of childbearing potential must be willing to use an&#xD;
             adequate method of contraception for the course of the study through 12 months after&#xD;
             the last dose of study treatment for participants who have received cyclophosphamide,&#xD;
             and 6 months after the last dose of study treatment for participants who did not.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of invasive malignancy ≤5 years prior to signing informed consent except&#xD;
             for adequately treated basal cell or squamous cell skin cancer or in situ cervical&#xD;
             cancer.&#xD;
&#xD;
          -  Has received prior chemotherapy, targeted therapy, and radiation therapy within the&#xD;
             past 12 months.&#xD;
&#xD;
          -  Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),&#xD;
             anti-programmed death - ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent&#xD;
             directed to another co-inhibitory T-cell receptor (e.g., cytotoxic&#xD;
             T-lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor&#xD;
             receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a&#xD;
             pembrolizumab (MK-3475) clinical study.&#xD;
&#xD;
          -  Is currently participating in or has participated in an interventional clinical study&#xD;
             with an investigational compound or device within 4 weeks of the first dose of&#xD;
             treatment in this current study.&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of the first dose of study treatment.&#xD;
&#xD;
          -  Has an active autoimmune disease that has required systemic treatment in past 2 years&#xD;
             (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs).&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e.,&#xD;
             dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study treatment.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
          -  Has known active Hepatitis B or Hepatitis C.&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has significant cardiovascular disease, such as: history of myocardial infarction,&#xD;
             acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the&#xD;
             last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA)&#xD;
             Class II-IV or history of CHF NYHA Class III or IV.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive children within the projected&#xD;
             duration of the study, starting with the screening visit through 12 months after the&#xD;
             last dose of study treatment for participants who have received cyclophosphamide, and&#xD;
             for 6 months after the last dose of study treatment for participants who have not.&#xD;
&#xD;
          -  Has a known hypersensitivity to the components of the study treatment or its analogs.&#xD;
&#xD;
          -  Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia G. Piper Cancer Center Pharmacy - Scottsdale Healthcare ( Site 0089)</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85268</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates PC- HOPE ( Site 8001)</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center ( Site 0091)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Cancer Care ( Site 0069)</name>
      <address>
        <city>Monterey</city>
        <state>California</state>
        <zip>93940</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICRI ( Site 0072)</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center ( Site 0021)</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine ( Site 0054)</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Hospital ( Site 0029)</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ of Miami-Sylvester Comprehensive Cancer Center- Kendall satellite ( Site 0079)</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Chicago Medical Center ( Site 0047)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1447</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Health System ( Site 0081)</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orchard Healthcare Research Inc. ( Site 0049)</name>
      <address>
        <city>Skokie</city>
        <state>Illinois</state>
        <zip>60077</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goshen Center for Cancer Care ( Site 0010)</name>
      <address>
        <city>Goshen</city>
        <state>Indiana</state>
        <zip>46526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospital and Clinics ( Site 0038)</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New England Cancer Specialists ( Site 0005)</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital ( Site 0003)</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology, PA ( Site 8013)</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey ( Site 0073)</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broome Oncology, LLC ( Site 8002)</name>
      <address>
        <city>Johnson City</city>
        <state>New York</state>
        <zip>13790</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nyack Hospital Infusion Center ( Site 0059)</name>
      <address>
        <city>Nyack</city>
        <state>New York</state>
        <zip>10960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0044)</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care, Inc. ( Site 8011)</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center ( Site 0052)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists, P.C. ( Site 8008)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee - Women's Hospital ( Site 0011)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital ( Site 0060)</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The West Clinic, P.C. ( Site 0078)</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Austin Central ( Site 8005)</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkland Health and Hospital System ( Site 0093)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8006)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Simmons Cancer Center ( Site 0094)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center ( Site 0030)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9179</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moncrief Cancer Institute ( Site 0092)</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Memorial City ( Site 8003)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Cancer Center ( Site 0013)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology- Plano East ( Site 8010)</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-San Antonio Northeast ( Site 8012)</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Tyler ( Site 8007)</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia ( Site 0022)</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists, PC ( Site 8009)</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Cancer Institute Medical Oncology at St. Mary's ( Site 0033)</name>
      <address>
        <city>Midlothian</city>
        <state>Virginia</state>
        <zip>23114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peninsula Cancer Institute, LLC ( Site 0041)</name>
      <address>
        <city>Newport News</city>
        <state>Virginia</state>
        <zip>23601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Oncology Associates ( Site 8000)</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kadlec Clinic Hematology and Oncology ( Site 0087)</name>
      <address>
        <city>Kennewick</city>
        <state>Washington</state>
        <zip>99336</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance ( Site 0068)</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Associates (Summit Cancer Centers) ( Site 0014)</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>YVMH dba Vrigina Mason Memorial/North Star Lodge Cancer Center ( Site 8004)</name>
      <address>
        <city>Yakima</city>
        <state>Washington</state>
        <zip>98902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital ( Site 2000)</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital ( Site 2002)</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital ( Site 2008)</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cabrini Health ( Site 2009)</name>
      <address>
        <city>East Malvern</city>
        <state>Victoria</state>
        <zip>3145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frankston Hospital ( Site 2010)</name>
      <address>
        <city>Franskton</city>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women s Hospital ( Site 2003)</name>
      <address>
        <city>Herston</city>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John of God Subiaco Hospital ( Site 2006)</name>
      <address>
        <city>Perth</city>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nossa Senhora da Conceicao ( Site 0203)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>91350-200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOPECCAN - Uniao Oeste Paranaense de Estudos e Combate ao Cancer ( Site 0206)</name>
      <address>
        <city>Cascavel</city>
        <zip>85806-300</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidade de Caxias do Sul ( Site 0201)</name>
      <address>
        <city>Caxias do Sul</city>
        <zip>95070-560</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Erasto Gaertner ( Site 0207)</name>
      <address>
        <city>Curitiba</city>
        <zip>81520-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto do Cancer do Ceara ( Site 0205)</name>
      <address>
        <city>Fortaleza</city>
        <zip>60430-230</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Araujo Jorge ( Site 0204)</name>
      <address>
        <city>Goiania</city>
        <zip>74605-070</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sao Lucas da PUCRS ( Site 0200)</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90610-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0208)</name>
      <address>
        <city>Sao Jose do Rio Preto</city>
        <zip>15090-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto do Cancer de Sao Paulo - ICESP ( Site 0211)</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01246-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre ( Site 0105)</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital - Cancer Care ( Site 0100)</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre ( Site 0103)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 0C1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital ( Site 0101)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIUSSS de l'Estrie-CHUS ( Site 0102)</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0104)</name>
      <address>
        <city>Quebec</city>
        <zip>G1S 4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncomedica S.A. ( Site 0404)</name>
      <address>
        <city>Monteria</city>
        <state>Cordoba</state>
        <zip>230002</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncologos del Occidente S.A. ( Site 0405)</name>
      <address>
        <city>Pereira</city>
        <state>Risaralda</state>
        <zip>661002</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario San Ignacio ( Site 0401)</name>
      <address>
        <city>Bogota</city>
        <zip>110231</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cancerologia [Bogota-Colombia] ( Site 0403)</name>
      <address>
        <city>Bogota</city>
        <zip>110411</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hemato Oncologos S.A. ( Site 0400)</name>
      <address>
        <city>Cali</city>
        <zip>760001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto De Cancerologia S.A. ( Site 0406)</name>
      <address>
        <city>Medellin</city>
        <zip>050024</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Jean Minjoz ( Site 0917)</name>
      <address>
        <city>Besancon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Polyclinique Bordeaux Nord Aquitaine ( Site 0911)</name>
      <address>
        <city>Bordeaux</city>
        <zip>33077</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Francois Baclesse ( Site 0907)</name>
      <address>
        <city>Caen</city>
        <zip>14000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Jean Perrin ( Site 0903)</name>
      <address>
        <city>Clermont-Ferrand Cedex 01</city>
        <zip>63001</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Victor Hugo ( Site 0901)</name>
      <address>
        <city>Le Mans</city>
        <zip>72015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital prive du Confluent ( Site 0902)</name>
      <address>
        <city>Nantes</city>
        <zip>44277</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie ( Site 0909)</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Louis ( Site 0908)</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Diaconesses Croix Saint Simon ( Site 0905)</name>
      <address>
        <city>Paris</city>
        <zip>75020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de la Miletrie Poitiers ( Site 0913)</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud IUCT Oncopole ( Site 0914)</name>
      <address>
        <city>Toulouse Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Klinikum Berlin-Buch ( Site 1005)</name>
      <address>
        <city>Berlin</city>
        <zip>13125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gynaekologisches Zentrum ( Site 1004)</name>
      <address>
        <city>Bonn</city>
        <zip>53111</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Erlangen ( Site 1001)</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kliniken Essen Mitte ( Site 1012)</name>
      <address>
        <city>Essen</city>
        <zip>45136</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinik und Poliklinik Halle/Saale ( Site 1008)</name>
      <address>
        <city>Halle</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Hamburg-Eppendorf ( Site 1007)</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universit. Muenchen ( Site 1002)</name>
      <address>
        <city>Muenchen</city>
        <zip>80337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Caritasklinik St. Theresia ( Site 1011)</name>
      <address>
        <city>Saarbruecken</city>
        <zip>66113</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaets-Frauenklinik Tuebingen ( Site 1003)</name>
      <address>
        <city>Tubingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Hospital ( Site 1551)</name>
      <address>
        <city>Cork</city>
        <zip>T12 DV56</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincents University Hospital ( Site 1550)</name>
      <address>
        <city>Dublin</city>
        <zip>D04 T6F4</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology institute ( Site 1601)</name>
      <address>
        <city>Beer Sheva</city>
        <zip>8410101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assaf Harofeh MC ( Site 1605)</name>
      <address>
        <city>Beer Yaakov-Zerifin</city>
        <zip>7030001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1600)</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin-Medical Center ( Site 1604)</name>
      <address>
        <city>Petah Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center ( Site 1602)</name>
      <address>
        <city>Ramat-Gan</city>
        <zip>5265601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Center ( Site 1603)</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1101)</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 1103)</name>
      <address>
        <city>Brescia</city>
        <zip>25100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Luca, AZIENDA USL2 TOSCANA NORD OVEST ( Site 1105)</name>
      <address>
        <city>Lucca</city>
        <zip>55100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile di Macerata ( Site 1104)</name>
      <address>
        <city>Macerata</city>
        <zip>62100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia ( Site 1106)</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1102)</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital ( Site 2502)</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East ( Site 2518)</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Hokkaido Cancer Center ( Site 2512)</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>003-0804</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hyogo College of Medicine Hospital ( Site 2506)</name>
      <address>
        <city>Nishinomiya</city>
        <state>Hyogo</state>
        <zip>663-8501</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokai University Hospital ( Site 2517)</name>
      <address>
        <city>Isehara</city>
        <state>Kanagawa</state>
        <zip>259-1193</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Marianna University School of Medicine Hospital ( Site 2516)</name>
      <address>
        <city>Kawasaki</city>
        <state>Kanagawa</state>
        <zip>216-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital ( Site 2507)</name>
      <address>
        <city>Osakasayama</city>
        <state>Osaka</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Medical University International Medical Center ( Site 2513)</name>
      <address>
        <city>Hidaka</city>
        <state>Saitama</state>
        <zip>350-1298</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Cancer Center ( Site 2510)</name>
      <address>
        <city>Kitaadachi-gun</city>
        <state>Saitama</state>
        <zip>362-0806</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shizuoka Cancer Center Hospital and Research Institute ( Site 2514)</name>
      <address>
        <city>Sunto-gun</city>
        <state>Shizuoka</state>
        <zip>411-8777</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiba Cancer Center ( Site 2519)</name>
      <address>
        <city>Chiba</city>
        <zip>260-8717</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hiroshima City Hiroshima Citizens Hospital ( Site 2501)</name>
      <address>
        <city>Hiroshima</city>
        <zip>730-8518</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Social medical corporation Hakuaikai Sagara Hospital ( Site 2508)</name>
      <address>
        <city>Kagoshima</city>
        <zip>892-0833</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kumamoto University Hospital ( Site 2515)</name>
      <address>
        <city>Kumamoto</city>
        <zip>860-8556</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Osaka National Hospital ( Site 2505)</name>
      <address>
        <city>Osaka</city>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital ( Site 2500)</name>
      <address>
        <city>Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St.Luke's International Hospital ( Site 2511)</name>
      <address>
        <city>Tokyo</city>
        <zip>104-8560</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toranomon Hospital ( Site 2503)</name>
      <address>
        <city>Tokyo</city>
        <zip>105-8470</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Institute Hospital of JFCR ( Site 2509)</name>
      <address>
        <city>Tokyo</city>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital ( Site 2101)</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital Yonsei University Health System ( Site 2100)</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center ( Site 2102)</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center ( Site 2103)</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mazowiecki Szpital Onkologiczny ( Site 1713)</name>
      <address>
        <city>Wieliszew</city>
        <state>Mazowieckie</state>
        <zip>05-135</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii Instytut im. Marii Skłodowskiej Curie ( Site 1717)</name>
      <address>
        <city>Gliwice</city>
        <state>Slaskie</state>
        <zip>44-101</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1708)</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-796</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1712)</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-796</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1701)</name>
      <address>
        <city>Gdynia</city>
        <zip>81-519</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1719)</name>
      <address>
        <city>Krakow</city>
        <zip>31-115</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1700)</name>
      <address>
        <city>Lublin</city>
        <zip>20-090</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dolnoslaskie Centrum Onkologii. ( Site 1702)</name>
      <address>
        <city>Wroclaw</city>
        <zip>53-413</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacao Champalimaud ( Site 2444)</name>
      <address>
        <city>Lisboa</city>
        <zip>1400-038</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Santa Maria, E.P.E. ( Site 2445)</name>
      <address>
        <city>Lisboa</city>
        <zip>1600-190</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2446)</name>
      <address>
        <city>Porto</city>
        <zip>4200-072</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkhangelsk Clinical Oncological Dispensary ( Site 1810)</name>
      <address>
        <city>Arkhangelsk</city>
        <zip>163045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1805)</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454087</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1806)</name>
      <address>
        <city>Kazan</city>
        <zip>420029</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1801)</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GBU RO Regional Clinical Oncological Dispensary ( Site 1808)</name>
      <address>
        <city>Ryazan</city>
        <zip>390046</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1803)</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1804)</name>
      <address>
        <city>Ufa</city>
        <zip>450054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Centre Singapore ( Site 2600)</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO L Hospitalet ( Site 1305)</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Quiron de Madrid ( Site 1303)</name>
      <address>
        <city>Pozuelo de Alarcon</city>
        <state>Madrid</state>
        <zip>28223</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar ( Site 1306)</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Oncologico Baselga.Hospital Quiron. ( Site 1312)</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitari Vall d Hebron ( Site 1301)</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofia ( Site 1304)</name>
      <address>
        <city>Cordoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal ( Site 1300)</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Santiago ( Site 1308)</name>
      <address>
        <city>Santiago de Compostela</city>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio ( Site 1314)</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Univ de Valencia ( Site 1313)</name>
      <address>
        <city>Valencia</city>
        <zip>46011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkopings Universitetssjukhus ( Site 1402)</name>
      <address>
        <city>Linkoping</city>
        <zip>581 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska Universitetssjukhuset Solna ( Site 1404)</name>
      <address>
        <city>Solna</city>
        <zip>171 64</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norrlands Universitetssjukhus ( Site 1401)</name>
      <address>
        <city>Umea</city>
        <zip>901 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akademiska Sjukhuset ( Site 1403)</name>
      <address>
        <city>Uppsala</city>
        <zip>751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital ( Site 2302)</name>
      <address>
        <city>Taipei</city>
        <state>Beitou</state>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital ( Site 2305)</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital ( Site 2301)</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MacKay Memorial Hospital ( Site 2303)</name>
      <address>
        <city>Taipei</city>
        <zip>105</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Koo Foundation Sun Yat-Sen Cancer Center ( Site 2304)</name>
      <address>
        <city>Taipei</city>
        <zip>11259</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital ( Site 2300)</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsun Ondokuz Mayıs Universitesi Tıp Fakultesi Hastanesi ( Site 1910)</name>
      <address>
        <city>Samsun</city>
        <state>Atakum</state>
        <zip>55280</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adana Acıbadem Hospital Department of Medical Oncology ( Site 1906)</name>
      <address>
        <city>Adana</city>
        <zip>01130</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baskent Unıversity Adana Kısla Hospital ( Site 1903)</name>
      <address>
        <city>Adana</city>
        <zip>01250</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1912)</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abdurrahman Yurtaslan Oncology Training and Research Hospital ( Site 1909)</name>
      <address>
        <city>Ankara</city>
        <zip>06200</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ozel Medicana International Ankara Hastanesi ( Site 1915)</name>
      <address>
        <city>Ankara</city>
        <zip>06510</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antalya Memorial Hospital Department of Medical Oncology ( Site 1908)</name>
      <address>
        <city>Antalya</city>
        <zip>07020</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1901)</name>
      <address>
        <city>Edirne</city>
        <zip>22030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acibadem Altunizade Hastanesi ( Site 1900)</name>
      <address>
        <city>Istambul</city>
        <zip>34662</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>İstanbul University Cerrahpaşa Medical Faculty ( Site 1904)</name>
      <address>
        <city>Istanbul</city>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amerikan Hospital Medical ( Site 1902)</name>
      <address>
        <city>Istanbul</city>
        <zip>34365</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sisli Hastanesi ( Site 1913)</name>
      <address>
        <city>Istanbul</city>
        <zip>34384</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1905)</name>
      <address>
        <city>Izmir</city>
        <zip>35040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Izmir Medical Park Hospital Department of Medical Oncology ( Site 1907)</name>
      <address>
        <city>Izmir</city>
        <zip>35575</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colchester General Hospital ( Site 1508)</name>
      <address>
        <city>Colchester</city>
        <state>Essex</state>
        <zip>CO4 5JL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Cancer Institute ( Site 1500)</name>
      <address>
        <city>London</city>
        <zip>EC1M 6BQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St George s Hospital ( Site 1516)</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maidstone Hospital ( Site 1511)</name>
      <address>
        <city>Maidstone</city>
        <zip>ME16 9QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The James Cook University Hospital ( Site 1515)</name>
      <address>
        <city>Middlesbrough</city>
        <zip>TS4 3BW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust ( Site 1505)</name>
      <address>
        <city>Nottingham</city>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospitals NHS Trust ( Site 1504)</name>
      <address>
        <city>Truro</city>
        <zip>TR1 3LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Colombia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Belgium</country>
    <country>Chile</country>
    <country>Denmark</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Peru</country>
  </removed_countries>
  <link>
    <url>https://www.merckclinicaltrials.com/</url>
    <description>Merck Clinical Trial Information</description>
  </link>
  <link>
    <url>https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=3475-522&amp;&amp;kw=3475-522</url>
    <description>Plain Language Summary</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PD1</keyword>
  <keyword>PD-1</keyword>
  <keyword>PDL1</keyword>
  <keyword>PD-L1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Lenograstim</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </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/NCT03036488
org study id: 3475-522
secondary id: 173567
secondary id: MK-3475-522
secondary id: KEYNOTE-522
secondary id: 2016-004740-11
nct id: NCT03036488
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475)
      plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs
      placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC).

      After a screening phase of approximately 28 days, each participant will receive neoadjuvant
      study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the
      randomization schedule for approximately 24 weeks (8 cycles). Each participant will then
      undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant
      study treatment. After definitive surgery, each participant will receive adjuvant study
      treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following
      adjuvant study treatment, each participant will be monitored for safety, survival and disease
      recurrence.

      The primary study hypothesis is that pembrolizumab is superior to placebo, in combination
      with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or
      Event-free Survival (EFS), in participants with locally advanced TNBC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
time frame: Up to approximately 27-30 weeks
description: pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
measure: Event-free Survival (EFS) as assessed by Investigator
time frame: Up to approximately 8 years
description: EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.
measure: pCR rate using an alternative definition, ypT0 ypN0 (i.e., no invasive or noninvasive residual in breast or nodes) at the time of definitive surgery
time frame: Up to approximately 27-30 weeks
description: pCR rate (ypT0 ypN0) is defined as the percentage of participants without residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing Programmed Death-Ligand 1 (PD-L1).
measure: pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
time frame: Up to approximately 27-30 weeks
description: pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in participants with tumors expressing PD-L1.
measure: EFS in participants with tumors expressing PD-L1
time frame: Up to approximately 8 years
description: EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.
measure: pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery
time frame: Up to approximately 27-30 weeks
description: pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing PD-L1.
measure: Overall survival (OS)
time frame: Up to approximately 8 years
description: OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis will be censored at the date of the last follow-up.
measure: Percentage of participants who experience an adverse event (AE)
time frame: Up to approximately 61 weeks
description: An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.
measure: Percentage of participants who discontinue study treatment due to an AE
time frame: Up to approximately 57 weeks
description: An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.
measure: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score
time frame: Up to approximately 27-30 weeks
description: The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-C30 score will be presented for all participants and for participants with tumors expressing PD-L1.
measure: EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) score
time frame: Up to approximately 27-30 weeks
description: The EORTC-QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life of breast cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-BR23 score will be presented for all participants and for participants with tumors expressing PD-L1.
arm group label: Pembrolizumab + Chemotherapy
arm group type: Experimental
description: Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.
arm group label: Placebo + Chemotherapy
arm group type: Active Comparator
description: Participants receive placebo (normal saline solution) Q3W + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by placebo + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of placebo Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.
intervention type: Biological
intervention name: Pembrolizumab
description: On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; intravenous (IV) infusion.
arm group label: Pembrolizumab + Chemotherapy
other name: MK-3475
other name: KEYTRUDA®
intervention type: Drug
intervention name: Carboplatin
description: On Day 1 of Cycles 1-4 of the neoadjuvant phase of the study OR on Days 1, 8, 15 of Cycles 1-4 of the neoadjuvant phase of the study; IV infusion.
arm group label: Pembrolizumab + Chemotherapy
arm group label: Placebo + Chemotherapy
other name: PARAPLATIN®
intervention type: Drug
intervention name: Paclitaxel
description: On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.
arm group label: Pembrolizumab + Chemotherapy
arm group label: Placebo + Chemotherapy
other name: TAXOL®
intervention type: Drug
intervention name: Doxorubicin
description: On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
arm group label: Pembrolizumab + Chemotherapy
arm group label: Placebo + Chemotherapy
other name: ADRIAMYCIN®
intervention type: Drug
intervention name: Epirubicin
description: On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
arm group label: Pembrolizumab + Chemotherapy
arm group label: Placebo + Chemotherapy
other name: ELLENCE®
intervention type: Drug
intervention name: Cyclophosphamide
description: On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.
arm group label: Pembrolizumab + Chemotherapy
arm group label: Placebo + Chemotherapy
other name: CYTOXAN®
intervention type: Drug
intervention name: Placebo
description: normal saline solution or dextrose: On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; IV infusion
arm group label: Placebo + Chemotherapy
intervention type: Biological
intervention name: Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim
description: For prevention of neutropenia, filgrastim 5 μg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgastrim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.
arm group label: Pembrolizumab + Chemotherapy
arm group label: Placebo + Chemotherapy
other name: NEUPOGEN®
other name: NEULASTA®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
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country: Australia
country: Brazil
country: Canada
country: Colombia
country: France
country: Germany
country: Ireland
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Poland
country: Portugal
country: Russian Federation
country: Singapore
country: Spain
country: Sweden
country: Taiwan
country: Turkey
country: United Kingdom
country: United States
country: Belgium
country: Chile
country: Denmark
country: Mexico
country: Netherlands
country: New Zealand
country: Peru
url: https://www.merckclinicaltrials.com/
description: Merck Clinical Trial Information
url: https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=3475-522&&kw=3475-522
description: Plain Language Summary
responsible party type: Sponsor
mesh term: Triple Negative Breast Neoplasms
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Carboplatin
mesh term: Doxorubicin
mesh term: Pembrolizumab
mesh term: Epirubicin
mesh term: Lenograstim
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php