<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/NCT03301350</url>
  </required_header>
  <id_info>
    <org_study_id>UW16112</org_study_id>
    <secondary_id>NCI-2017-01705</secondary_id>
    <secondary_id>2017-0547</secondary_id>
    <secondary_id>A534260</secondary_id>
    <secondary_id>SMPH\MEDICINE\HEM-ONC</secondary_id>
    <secondary_id>Protocol Version 11/26/2019</secondary_id>
    <nct_id>NCT03301350</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer</brief_title>
  <official_title>A Phase II Study of Neoadjuvant Carboplatin/Paclitaxel Followed by Dose-Dense Doxorubicin/Cyclophosphamide in Patients With Hormone Receptor Negative, HER2 Receptor Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the&#xD;
      low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in&#xD;
      subjects with triple-negative breast cancer in neoadjuvant settings.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2017</start_date>
  <completion_date type="Actual">February 7, 2022</completion_date>
  <primary_completion_date type="Actual">March 23, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>pCR is defined as the absence of 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. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Cycles of Chemotherapy Administered</measure>
    <time_frame>Week 12 to week 18 to account for possible delays</time_frame>
    <description>To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Dose of Chemotherapy Administered</measure>
    <time_frame>Week 12 to week 18 to account for possible delays</time_frame>
    <description>To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delays of Administered Chemotherapy</measure>
    <time_frame>Week 12 to week 18 to account for possible delays</time_frame>
    <description>To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment-related Toxicities Experienced by Participants</measure>
    <time_frame>Up to week 12</time_frame>
    <description>Count of any treatment-related toxicities from the low dose weekly Carboplatin/Paclitaxel regimen. Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free Survival (RFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To evaluate two-year RFS after treatment with this neoadjuvant regimen. Count of participants without evidence for local-regional or distant relapse, second primary, or death will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. Count of participants who achieved 2 year OS is reported.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links.</description>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.</description>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.</description>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
    <other_name>Adriamycin</other_name>
    <other_name>Doxil</other_name>
    <other_name>Caelyx</other_name>
    <other_name>Myocet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver.</description>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
    <other_name>cytophosphane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegfilgrastim</intervention_name>
    <description>Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.</description>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Filgrastim</intervention_name>
    <description>Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.</description>
    <arm_group_label>Neoadjuvant Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects must have histologically or cytologically confirmed invasive breast cancer&#xD;
             which meets the following criteria:&#xD;
&#xD;
               1. Estrogen Receptor (ER) and Progesterone Receptor (PR)-negative as defined by&#xD;
                  local standard clinical immunohistochemistry (IHC) &lt; 1%.&#xD;
&#xD;
               2. HER2-negative using local standard testing. Negative is defined as IHC 0 or 1+&#xD;
                  (if 2+, must reflex to ISH method). If ISH method is used, ratio &lt; 2 is&#xD;
                  considered negative.&#xD;
&#xD;
               3. Clinical tumor size of at least 2.1 cm (T2) by palpation or imaging, regardless&#xD;
                  of the ipsilateral regional lymph node status, or any tumor size but with&#xD;
                  ipsilateral regional lymph nodes involved by the tumor (any T if ipsilateral&#xD;
                  regional node positive). Subjects with inflammatory breast cancer are eligible.&#xD;
                  If bilateral breast cancer is present, the subject is eligible if the&#xD;
                  contralateral tumor is DCIS only (without any invasive disease on biopsy) or&#xD;
                  another invasive breast cancer of any size that is also ER, PR and HER2 negative.&#xD;
&#xD;
               4. Any radiographic abnormal ipsilateral regional lymph nodes or any clinically&#xD;
                  concerning ipsilateral regional lymph nodes with the exception of internal&#xD;
                  mammary nodes should be sampled with percutaneous biopsy, but no sentinel&#xD;
                  axillary lymph node mapping/biopsy is allowed before chemotherapy. If clinically&#xD;
                  node negative (cNO), pre-chemotherapy ipsilateral sentinel axillary lymph node&#xD;
                  mapping/biopsy is not allowed.&#xD;
&#xD;
          2. Candidate for neoadjuvant chemotherapy.&#xD;
&#xD;
          3. Age &gt; 18 years and &lt; 75 years&#xD;
&#xD;
          4. ECOG Performance Status &lt; 1.&#xD;
&#xD;
          5. Left ventricular ejection fraction (LVEF) ≥ LLN (per institutional normal) determined&#xD;
             by&#xD;
&#xD;
          6. Adequate organ and marrow function as determined by study protocol&#xD;
&#xD;
          7. Non Pregnant. Women of childbearing potential must have a negative pregnancy test (HCG&#xD;
             serum or urine) within 30 days prior to study registration and to be repeated if not&#xD;
             done within 7 days of starting chemotherapy.&#xD;
&#xD;
               1. Female subjects must meet one of the following:&#xD;
&#xD;
                    -  Natural postmenopausal before the screening visit defined as no menses at&#xD;
                       any time in the preceding 12 consecutive months, or&#xD;
&#xD;
                    -  Prior bilateral oophorectomy or bilateral tubal ligation, or&#xD;
&#xD;
                    -  If they are of childbearing potential, agree to practice two effective&#xD;
                       methods of contraception per discussion with the treating physicians from&#xD;
&#xD;
               2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must&#xD;
                  agree to one of the following:&#xD;
&#xD;
                    -  Practice effective barrier contraception during the entire study treatment&#xD;
                       period and through 90 days after the last study drug dose, or&#xD;
&#xD;
                    -  Agree to practice true abstinence when this is in line with the preferred&#xD;
                       and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar,&#xD;
                       ovulation, symptothermal, postovulation methods] and withdrawal are not&#xD;
                       acceptable methods of contraception.)&#xD;
&#xD;
          8. Ability to understand a written informed consent document, and the willingness to sign&#xD;
             it.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior chemotherapy or radiation therapy for invasive breast cancer within 6 months&#xD;
             before registration.&#xD;
&#xD;
          2. Prior investigational drugs or interventions for invasive breast cancer within 6&#xD;
             months before registration are not allowed. Prior participation in&#xD;
             window-of-opportunity trials without therapeutic intent is allowed if intervention is&#xD;
             no more than 3 weeks duration.&#xD;
&#xD;
          3. Stage IV metastatic breast cancer&#xD;
&#xD;
          4. History of allergic reactions attributed to compounds of similar chemical composition&#xD;
             to chemotherapy to be used in this study.&#xD;
&#xD;
          5. Breastfeeding women. Cytotoxic chemotherapy is drug with the potential for teratogenic&#xD;
             or abortifacient effects. Due to unknown but potential risk for adverse events in&#xD;
             nursing infants secondary to treatment of the mother with cytotoxic chemotherapy,&#xD;
             breastfeeding should be discontinued.&#xD;
&#xD;
          6. Baseline peripheral neuropathy of severity &gt; grade 1&#xD;
&#xD;
          7. Other invasive cancer diagnosis within the past 5 years other than non-melanoma skin&#xD;
             cancer.&#xD;
&#xD;
          8. Prior axillary lymph node dissection that preclude patient from surgical evaluation of&#xD;
             axillary lymph node status.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kari Wisinski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Swedish American Hospital</name>
      <address>
        <city>Rockford</city>
        <state>Illinois</state>
        <zip>61104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia St. Mary's Cancer Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProHealth Care</name>
      <address>
        <city>Waukesha</city>
        <state>Wisconsin</state>
        <zip>53188</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aspirus Regional Cancer Center Wausau</name>
      <address>
        <city>Wausau</city>
        <state>Wisconsin</state>
        <zip>54401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.uwhealth.org/uw-carbone-cancer-center/47424</url>
    <description>UW Carbone Cancer Center home page</description>
  </link>
  <link>
    <url>https://www.mcw.edu/Cancer-Center.htm</url>
    <description>Medical College of Wisconsin Cancer Center page</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <results_first_submitted>October 14, 2022</results_first_submitted>
  <results_first_submitted_qc>January 9, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 1, 2023</results_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative 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>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03301350/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>29 participants were assigned, but only 28 participants started treatment</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Neoadjuvant Chemotherapy</title>
          <description>Participants receive Paclitaxel and Carboplatin AUC=2 on days 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks).&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Participants receive Doxorubicin and Cyclophosphamide on day 1 of cycles 5, 6, 7, 8 (every 2 weeks). Participants also receive Pegfilgrastim, filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
Participants undergo surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pt withdrawn per DSMC request</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>completed all chemo cycles, however died prior to definitive surgery</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>no detail provided</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>1 participant withdrew after being assigned but prior to treatment. Characteristics were collected for baseline hence 29 baseline participants being reported</population>
      <group_list>
        <group group_id="B1">
          <title>Neoadjuvant Chemotherapy</title>
          <description>Paclitaxel (cycles 1-4):&#xD;
Doxorubicin, Cyclophosphamide, and Pegfilgrastim (cycles 5-8):&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>30-39</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40-49</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50-59</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>80-89</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate</title>
        <description>pCR is defined as the absence of 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. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>4 participants did not reach the timepoint at which pCR was measured, therefore are not counted in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Participants receive Paclitaxel and Carboplatin AUC=2 on days 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks).&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Participants receive Doxorubicin and Cyclophosphamide on day 1 of cycles 5, 6, 7, 8 (every 2 weeks). Participants also receive Pegfilgrastim, filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
Participants undergo surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate</title>
          <description>pCR is defined as the absence of 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. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.</description>
          <population>4 participants did not reach the timepoint at which pCR was measured, therefore are not counted in the analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Cycles of Chemotherapy Administered</title>
        <description>To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered.</description>
        <time_frame>Week 12 to week 18 to account for possible delays</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Cycles of Chemotherapy Administered</title>
          <description>To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4 complete cycles</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Less than 1 cycle</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Dose of Chemotherapy Administered</title>
        <description>To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered.</description>
        <time_frame>Week 12 to week 18 to account for possible delays</time_frame>
        <population>2 participants were withdrawn from study prior to completing carbo-paclitaxel; thus, have not been included in this measure</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Dose of Chemotherapy Administered</title>
          <description>To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered.</description>
          <population>2 participants were withdrawn from study prior to completing carbo-paclitaxel; thus, have not been included in this measure</population>
          <units>doses administered</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Carboplatin dose AUC of 2.0 - full dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>paclitaxel dose: 80 mg/m2 - full dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="279"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Carboplatin reduced dose AUC 1.6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Carboplatin reduced dose AUC 1.5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Paclitaxel - reduced dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Delays of Administered Chemotherapy</title>
        <description>To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered.</description>
        <time_frame>Week 12 to week 18 to account for possible delays</time_frame>
        <population>2 participants were withdrawn from study prior to completing carbo-paclitaxel; thus, have not been included in this measure</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Delays of Administered Chemotherapy</title>
          <description>To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered.</description>
          <population>2 participants were withdrawn from study prior to completing carbo-paclitaxel; thus, have not been included in this measure</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with no delays</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with single 1 week delay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with single 2 week delay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with more than 1 delay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment-related Toxicities Experienced by Participants</title>
        <description>Count of any treatment-related toxicities from the low dose weekly Carboplatin/Paclitaxel regimen. Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
        <time_frame>Up to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-related Toxicities Experienced by Participants</title>
          <description>Count of any treatment-related toxicities from the low dose weekly Carboplatin/Paclitaxel regimen. Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0</description>
          <units>treatment related toxicities</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Neutrophil count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cells decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Recurrence-free Survival (RFS)</title>
        <description>To evaluate two-year RFS after treatment with this neoadjuvant regimen. Count of participants without evidence for local-regional or distant relapse, second primary, or death will be reported.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>4 participants did not reach the timepoint at which RFS was measured, therefore are not counted in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Recurrence-free Survival (RFS)</title>
          <description>To evaluate two-year RFS after treatment with this neoadjuvant regimen. Count of participants without evidence for local-regional or distant relapse, second primary, or death will be reported.</description>
          <population>4 participants did not reach the timepoint at which RFS was measured, therefore are not counted in the analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No evidence of disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Alive, recurrent disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Deceased, recurrent disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Alive, unknown disease status</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. Count of participants who achieved 2 year OS is reported.</description>
        <time_frame>Up to 2 years</time_frame>
        <population>3 participants did not reach the timepoint at which OS was measured, therefore are not counted in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Chemotherapy</title>
            <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. Count of participants who achieved 2 year OS is reported.</description>
          <population>3 participants did not reach the timepoint at which OS was measured, therefore are not counted in the analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>2 year survival</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Deceased</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years from starting study treatment</time_frame>
      <desc>Other (Not Including Serious) Adverse Events were not collected/monitored at collaborating site for 18 of the participants; therefore, there is no data to report and the number assessed is most accurately represented as 10 at risk for Other Adverse Events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Neoadjuvant Chemotherapy</title>
          <description>Regimen A (cycles 1-4):&#xD;
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)&#xD;
Regimen B (cycles 5-8):&#xD;
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)&#xD;
There is a one week break between the end of cycle 4 and the beginning of cycle 5.&#xD;
Regimen C:&#xD;
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="28"/>
              </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" events="5" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrilation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdomincal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Vascular access complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>platelet count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="39" subjects_affected="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Conjuntivitis infective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fecal incontinence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Generalized edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thrush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Conjunctivitis infective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="33" subjects_affected="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="18" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="53" subjects_affected="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT corrected interval prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hemoglobinuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nail discoloration</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nail changes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nail loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nail ridging</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Complete AE data was not collected; approximately 40% of participants are represented in the data reported in the Adverse Events section. Some enrolling sites have been chronically under- and un-staffed for 2+ years, and have not been able to address the coordinating center's numerous queries related to AE data.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Kari Wisinski, MD</name_or_title>
      <organization>University of Wisconsin Carbone Cancer Center</organization>
      <phone>608-262-2876</phone>
      <email>kbwisinski@medicine.wisc.edu</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/NCT03301350
org study id: UW16112
secondary id: NCI-2017-01705
secondary id: 2017-0547
secondary id: A534260
secondary id: SMPH\MEDICINE\HEM-ONC
secondary id: Protocol Version 11/26/2019
nct id: NCT03301350
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the
      low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in
      subjects with triple-negative breast cancer in neoadjuvant settings.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate
time frame: Up to 2 years
description: pCR is defined as the absence of 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. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.
measure: Number of Cycles of Chemotherapy Administered
time frame: Week 12 to week 18 to account for possible delays
description: To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered.
measure: Total Dose of Chemotherapy Administered
time frame: Week 12 to week 18 to account for possible delays
description: To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered.
measure: Delays of Administered Chemotherapy
time frame: Week 12 to week 18 to account for possible delays
description: To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered.
measure: Number of Treatment-related Toxicities Experienced by Participants
time frame: Up to week 12
description: Count of any treatment-related toxicities from the low dose weekly Carboplatin/Paclitaxel regimen. Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
measure: Recurrence-free Survival (RFS)
time frame: Up to 2 years
description: To evaluate two-year RFS after treatment with this neoadjuvant regimen. Count of participants without evidence for local-regional or distant relapse, second primary, or death will be reported.
measure: Overall Survival (OS)
time frame: Up to 2 years
description: To evaluate the two-year overall survival after treatment with this neoadjuvant regimen. Count of participants who achieved 2 year OS is reported.
arm group label: Neoadjuvant Chemotherapy
arm group type: Experimental
description: Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links.
arm group label: Neoadjuvant Chemotherapy
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.
arm group label: Neoadjuvant Chemotherapy
intervention type: Drug
intervention name: Doxorubicin
description: Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.
arm group label: Neoadjuvant Chemotherapy
other name: Adriamycin
other name: Doxil
other name: Caelyx
other name: Myocet
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver.
arm group label: Neoadjuvant Chemotherapy
other name: cytophosphane
intervention type: Drug
intervention name: Pegfilgrastim
description: Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.
arm group label: Neoadjuvant Chemotherapy
intervention type: Drug
intervention name: Filgrastim
description: Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.
arm group label: Neoadjuvant Chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Kari Wisinski, MD
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.uwhealth.org/uw-carbone-cancer-center/47424
description: UW Carbone Cancer Center home page
url: https://www.mcw.edu/Cancer-Center.htm
description: Medical College of Wisconsin Cancer Center page
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Carboplatin
mesh term: Doxorubicin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Complete AE data was not collected; approximately 40% of participants are represented in the data reported in the Adverse Events section. Some enrolling sites have been chronically under- and un-staffed for 2+ years, and have not been able to address the coordinating center's numerous queries related to AE data.
point of contact: 