<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/NCT01705691</url>
  </required_header>
  <id_info>
    <org_study_id>NSABP FB-9</org_study_id>
    <nct_id>NCT01705691</nct_id>
  </id_info>
  <brief_title>Comparison of Neoadjuvant Chemotherapy With Weekly Paclitaxel or Eribulin Followed by A/C in Women With Locally Advanced HER2-Negative Breast Cancer</brief_title>
  <official_title>A Phase II Randomized Clinical Trial Evaluating Neoadjuvant Chemotherapy Regimens With Weekly Paclitaxel or Eribulin Followed by Doxorubicin and Cyclophosphamide in Women With Locally Advanced HER2-Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NSABP Foundation Inc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NSABP Foundation Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      NSABP FB-9 is a Phase II, multi-center, randomized study of eribulin or weekly paclitaxel&#xD;
      followed by doxorubicin and cyclophosphamide (AC) as neoadjuvant therapy for women with&#xD;
      HER2-negative, operable and locally advanced breast cancer (stage IIb and III). Patients in&#xD;
      the control arm will receive neoadjuvant weekly paclitaxel (WP) followed by AC. The primary&#xD;
      aim of the study is to determine the pathologic complete response (ypCR) in breast and&#xD;
      axillary lymph nodes following completion of neoadjuvant therapy. The secondary aims include&#xD;
      determination of the ypCR in axillary nodes, clinical complete response (ycCR) rate after&#xD;
      eribulin or paclitaxel and after completion of neoadjuvant chemotherapy, two-year&#xD;
      recurrence-free interval, two-year overall survival, and toxicity of the neoadjuvant&#xD;
      regimens.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be randomized to one of two neoadjuvant therapy regimens. Patients in Arm 1&#xD;
      will receive WP 80 mg/m2 for 12 doses followed by standard AC every 21 days for 4 cycles.&#xD;
      Patients in Arm 2 will receive 4 cycles of eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day&#xD;
      cycle followed by standard AC every 21 days for 4 cycles. As soon as possible following&#xD;
      recovery from chemotherapy, the patient will have either lumpectomy or mastectomy and&#xD;
      axillary staging.&#xD;
&#xD;
      In both arms, clinical response will be assessed by physical exam on day 1 of each study&#xD;
      therapy cycle. MRI of the breast is required within 4 weeks prior to randomization and&#xD;
      following completion of eribulin or WP (before starting AC). Following recovery from surgery,&#xD;
      patients will receive radiation therapy and hormonal therapy as clinically indicated. Other&#xD;
      postoperative therapies are prohibited.&#xD;
&#xD;
      Patients will be randomized to the control arm (Arm 1) and to the investigational arm (Arm 2)&#xD;
      in a 1:2 ratio. The sample size will be up to 50 patients with about 30 patients in Arm 2 and&#xD;
      about half that number in Arm 1. Accrual is expected to occur over 15 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathologic Complete Response Rate (ypCR) Following Neoadjuvant Therapy in Breast and Axillary Lymph Nodes</measure>
    <time_frame>At the time of surgery approximately 24 to 28 weeks.</time_frame>
    <description>Percentage of patients with no histologic evidence of cancer in breast and axillary lymph nodes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ypCR Nodes</measure>
    <time_frame>At the time of surgery approximately 24 to 28 weeks.</time_frame>
    <description>Percentage of patients with no histologic evidence of cancer in axillary lymph nodes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Overall Response (cOR)(Complete and Partial) Assessed by MRI at the Completion of WP or Eribulin (Before AC)</measure>
    <time_frame>12 weeks after initiation of study therapy</time_frame>
    <description>Percentage of patients with clinical complete response (no significant enhancement on MR images) or clinical partial response (at least 30% decrease in the maximal diameter of the tumor)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Complete Response (ycCR) Following Neoadjuvant Therapy Assessed by Physical Exam at the Completion of Neoadjuvant Chemotherapy</measure>
    <time_frame>At approximately 24 to 28 weeks from initiation of study therapy</time_frame>
    <description>The number of patients with clinical complete response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence Free Interval (RFI): The Time to Occurrence of Inoperable Progressive Disease and Local, Regional, and Distant Recurrence.</measure>
    <time_frame>Assessed through 24 months from randomization</time_frame>
    <description>The percentage of patients free from recurrence at 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-year Overall Survival (OS): Death From Any Cause From Time of Randomization Through 2 Years After Randomization.</measure>
    <time_frame>Assessed through 24 months from randomization</time_frame>
    <description>Percentage of patients alive at 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events Experienced by Participants as a Measure of Toxicity.</measure>
    <time_frame>Assessed through 24 months from randomization</time_frame>
    <description>Total patients with at least 1 AE.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Breast Cancer</condition>
  <condition>HER2-negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1: Paclitaxel then AC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: Eribulin then AC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>80 mg/m2 IV over 60 minutes weekly for 12 weeks</description>
    <arm_group_label>Arm 1: Paclitaxel then AC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eribulin</intervention_name>
    <description>1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles</description>
    <arm_group_label>Arm 2: Eribulin then AC</arm_group_label>
    <other_name>eribulin mesylate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles</description>
    <arm_group_label>Arm 1: Paclitaxel then AC</arm_group_label>
    <arm_group_label>Arm 2: Eribulin then AC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
    <arm_group_label>Arm 1: Paclitaxel then AC</arm_group_label>
    <arm_group_label>Arm 2: Eribulin then AC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients should have a life expectancy of at least 10 years, excluding their diagnosis&#xD;
             of breast cancer. (Comorbid conditions should be taken into consideration, but not the&#xD;
             diagnosis of breast cancer.)&#xD;
&#xD;
          -  Patients of reproductive potential must agree to use an effective non-hormonal method&#xD;
             of contraception during therapy and for at least 6 months after the last dose of study&#xD;
             therapy.&#xD;
&#xD;
          -  The patient must have consented to participate and must have signed and dated an&#xD;
             appropriate Institutional Review Board (IRB)-approved consent form that conforms to&#xD;
             federal and institutional guidelines.&#xD;
&#xD;
          -  Patients must be female.&#xD;
&#xD;
          -  Patients must be &gt; 18 years old.&#xD;
&#xD;
          -  The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.&#xD;
&#xD;
          -  The diagnosis of invasive adenocarcinoma of the breast must have been made by core&#xD;
             needle biopsy or by limited incisional biopsy.&#xD;
&#xD;
          -  Patients must have ER analysis performed on the primary tumor prior to randomization.&#xD;
             If ER analysis is negative, then Progesterone Receptor (PgR) analysis must also be&#xD;
             performed. (Patients are eligible with either hormone receptor-positive or hormone&#xD;
             receptor-negative tumors.)&#xD;
&#xD;
          -  Clinical staging, based on the assessment by physical exam, must be American Joint&#xD;
             Committee on Cancer (AJCC) stage IIB, IIIA, IIIB, or IIIC: cT2 and cN1, cT3 and cN0 or&#xD;
             cN1, Any cT and cN2 or cN3, cT4&#xD;
&#xD;
          -  The patient must have a mass in the breast or axilla measuring greater than or equal&#xD;
             to 2.0 cm by physical exam, unless the patient has inflammatory breast cancer, in&#xD;
             which case measurable disease by physical exam is not required.&#xD;
&#xD;
          -  At the time of randomization, blood counts performed within 4 weeks prior to&#xD;
             randomization must meet the following criteria: Absolute Neutrophil Count (ANC) must&#xD;
             be greater than or equal to 1200/mm3; Platelet count must be greater than or equal to&#xD;
             100,000/mm3; Hemoglobin must be greater than or equal to 10 g/dL.&#xD;
&#xD;
          -  The following criteria for evidence of adequate hepatic function performed within 4&#xD;
             weeks prior to randomization must be met: total bilirubin must be less than or equal&#xD;
             to Upper Limit of Normal (ULN) for the lab unless the patient has a bilirubin&#xD;
             elevation &gt; ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving&#xD;
             slow conjugation of bilirubin; and alkaline phosphatase must be less than or equal to&#xD;
             1.5 x ULN for the lab; and Aspartate aminotransferase (AST) and Alanine&#xD;
             aminotransferase (ALT) must be less than or equal to 1.5 x ULN for the lab.&#xD;
&#xD;
          -  Patients with alkaline phosphatase &gt; ULN but less than or equal to 1.5 x ULN are&#xD;
             eligible for inclusion in the study if liver imaging (CT, MRI, PET, or PET-CT scan)&#xD;
             performed within 4 weeks prior to randomization does not demonstrate metastatic&#xD;
             disease and the requirements in the criteria below for unexplained skeletal pain are&#xD;
             met.&#xD;
&#xD;
          -  Patients with either unexplained skeletal pain or alkaline phosphatase that is &gt; ULN&#xD;
             but less than or equal to 1.5 x ULN are eligible for inclusion in the study if a bone&#xD;
             scan, PET-CT scan, or PET scan performed within 4 weeks prior to randomization does&#xD;
             not demonstrate metastatic disease. Patients with suspicious findings on bone scan or&#xD;
             PET scan are eligible if suspicious findings are determined to be benign by x-ray,&#xD;
             MRI, or biopsy.&#xD;
&#xD;
          -  Serum creatinine performed within 4 weeks prior to randomization must be less than or&#xD;
             equal to 1.5 x ULN for the lab.&#xD;
&#xD;
          -  Serum potassium and serum magnesium performed within 4 weeks prior to randomization&#xD;
             must be Within Normal Limits (WNL).&#xD;
&#xD;
          -  The Left Ventricular Ejection Fraction (LVEF) assessment by 2-D echocardiogram or&#xD;
             Multigated acquisition (MUGA) scan performed within 90 days prior to randomization&#xD;
             must be greater than or equal to 50% regardless of the facility's Lower Limit of&#xD;
             Normal (LLN).&#xD;
&#xD;
          -  ECG performed within 4 weeks before study entry must demonstrate a QTc interval that&#xD;
             is less than or equal to 0.47 seconds.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Tumor that has been determined to be HER2-positive by immunohistochemistry (3+) or by&#xD;
             in situ hybridization (positive for gene amplification), or has been determined to be&#xD;
             HER2-equivocal and the investigator plans to administer trastuzumab or other targeted&#xD;
             therapy.&#xD;
&#xD;
          -  Fine Needle Aspiration (FNA) alone to diagnose the primary breast cancer.&#xD;
&#xD;
          -  Excisional biopsy or lumpectomy performed prior to randomization.&#xD;
&#xD;
          -  Surgical axillary staging procedure prior to randomization. (Procedures that are&#xD;
             permitted prior to study entry include: 1) FNA or core biopsy of an axillary node for&#xD;
             any patient, and 2) although not recommended, a pre-neoadjuvant therapy Sentinal Node&#xD;
             (SN) biopsy for patients with clinically negative axillary nodes.)&#xD;
&#xD;
          -  Definitive clinical or radiologic evidence of metastatic disease. (Note: Chest imaging&#xD;
             is mandatory for all patients within 90 days prior to randomization. Other imaging [if&#xD;
             required] must have been performed within 4 weeks prior to randomization.)&#xD;
&#xD;
          -  History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral&#xD;
             Ductal Carcinoma in Situ (DCIS) treated with Radiation Therapy (RT). (Patients with a&#xD;
             history of Lobular Carcinoma in Situ (LCIS), contralateral DCIS [regardless of RT], or&#xD;
             contralateral invasive breast cancer are eligible.)&#xD;
&#xD;
          -  History of non-breast malignancies (except for in situ cancers treated only by local&#xD;
             excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior&#xD;
             to randomization.&#xD;
&#xD;
          -  Known metastatic disease from any malignancy (solid tumor or hematologic).&#xD;
&#xD;
          -  Previous therapy with anthracyclines, taxanes, cyclophosphamide, or eribulin for any&#xD;
             malignancy.&#xD;
&#xD;
          -  Treatment including RT, chemotherapy, and/or targeted therapy, administered for the&#xD;
             currently diagnosed breast cancer prior to randomization.&#xD;
&#xD;
          -  Continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an&#xD;
             aromatase inhibitor. (Patients are eligible if these medications are discontinued&#xD;
             prior to randomization.)&#xD;
&#xD;
          -  Any continued sex hormonal therapy, e.g., birth control pills and ovarian hormone&#xD;
             replacement therapy. Patients are eligible if these medications are discontinued prior&#xD;
             to randomization.&#xD;
&#xD;
          -  Requirement for chronic use of any drugs known to prolong the QT interval, including&#xD;
             Na+ and K+ channel blockers. (Patients are eligible if these medications and/or&#xD;
             substances can be discontinued prior to the first dose of eribulin and will not need&#xD;
             to be resumed until after the last dose of eribulin.)&#xD;
&#xD;
          -  Active hepatitis B or hepatitis C with abnormal liver function tests.&#xD;
&#xD;
          -  Intrinsic lung disease resulting in dyspnea.&#xD;
&#xD;
          -  Active infection; or chronic infection requiring chronic suppressive antibiotics.&#xD;
&#xD;
          -  Persistent greater than or equal to grade 2 diarrhea regardless of etiology.&#xD;
&#xD;
          -  Sensory or motor neuropathy greater than or equal to grade 2, as defined by the NCI&#xD;
             Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.&#xD;
&#xD;
          -  Conditions that would prohibit intermittent administration of corticosteroids for&#xD;
             paclitaxel premedication.&#xD;
&#xD;
          -  Chronic daily treatment with corticosteroids with a dose of greater than or equal to&#xD;
             10 mg/day methylprednisolone equivalent (excluding inhaled steroids).&#xD;
&#xD;
          -  Uncontrolled hypertension defined as a systolic BP &gt; 150 mmHg or diastolic BP &gt; 90&#xD;
             mmHg, with or without anti-hypertensive medications. (Patients with hypertension that&#xD;
             is well-controlled on medication are eligible.)&#xD;
&#xD;
          -  Cardiac disease (history of and/or active disease) that would preclude the use of any&#xD;
             of the drugs included in the treatment regimen. This includes but is not confined to:&#xD;
             Active cardiac disease: symptomatic angina pectoris within the past 180 days that&#xD;
             required the initiation of or increase in anti-anginal medication or other&#xD;
             intervention; ventricular arrhythmias except for benign premature ventricular&#xD;
             contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not&#xD;
             controlled with medication; conduction abnormality requiring a pacemaker; valvular&#xD;
             disease with documented compromise in cardiac function; and symptomatic pericarditis.&#xD;
             History of cardiac disease: myocardial infarction documented by elevated cardiac&#xD;
             enzymes or persistent regional wall abnormalities on assessment of Left Ventricular&#xD;
             (LV) function; history of documented Congestive Heart Failure (CHF) documented&#xD;
             cardiomyopathy; and congenital long QT syndrome.&#xD;
&#xD;
          -  Other nonmalignant systemic disease that would preclude the patient from receiving&#xD;
             study treatment or would prevent required follow-up.&#xD;
&#xD;
          -  Pregnancy or lactation at the time of randomization.&#xD;
&#xD;
          -  Any psychiatric or addictive disorder or other condition that, in the opinion of the&#xD;
             investigator, would preclude her from meeting the study requirements.&#xD;
&#xD;
          -  Use of any investigation agent within 4 weeks prior to randomization.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Norman Wolmark, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NSABP Foundation Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CCOP, Colorado Cancer Research Program, Inc.</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80222</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CCOP - Mount Sinai Medical Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Phoebe Putney Memorial Hospital</name>
      <address>
        <city>Albany</city>
        <state>Georgia</state>
        <zip>31703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Health University Medical Center</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Hospital - Southfield</name>
      <address>
        <city>Southfield</city>
        <state>Michigan</state>
        <zip>48075-9975</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center/Levine Cancer Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital/Allegheny-Singer Research Institute</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NSABP Foundation, Inc.</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232-1305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roper Hospital</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Centers of the Carolinas</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Joe Arrington Cancer Research &amp; Treatment Center</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Babb Randolph Cancer Center at West Virginia University Hospitals</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Universite de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W-1T8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3G 1A4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <results_first_submitted>August 9, 2018</results_first_submitted>
  <results_first_submitted_qc>September 14, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 18, 2018</results_first_posted>
  <last_update_submitted>October 4, 2021</last_update_submitted>
  <last_update_submitted_qc>October 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2021</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>
  </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>Doxorubicin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>One patient randomly assigned to Arm 2 withdrew consent before receiving protocol therapy.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm 1: Paclitaxel Then AC</title>
          <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
        </group>
        <group group_id="P2">
          <title>Arm 2: Eribulin Then AC</title>
          <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm 1: Paclitaxel Then AC</title>
          <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
        </group>
        <group group_id="B2">
          <title>Arm 2: Eribulin Then AC</title>
          <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="49"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.47" spread="10.73"/>
                    <measurement group_id="B2" value="49.17" spread="13.21"/>
                    <measurement group_id="B3" value="49.67" spread="12.21"/>
                  </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="19"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown Ethnicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pathologic Complete Response Rate (ypCR) Following Neoadjuvant Therapy in Breast and Axillary Lymph Nodes</title>
        <description>Percentage of patients with no histologic evidence of cancer in breast and axillary lymph nodes.</description>
        <time_frame>At the time of surgery approximately 24 to 28 weeks.</time_frame>
        <population>1 patient in Arm 1 was not analyzed due to inoperable, progressive disease. 2 patients in Arm 2 are missing data.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Pathologic Complete Response Rate (ypCR) Following Neoadjuvant Therapy in Breast and Axillary Lymph Nodes</title>
          <description>Percentage of patients with no histologic evidence of cancer in breast and axillary lymph nodes.</description>
          <population>1 patient in Arm 1 was not analyzed due to inoperable, progressive disease. 2 patients in Arm 2 are missing data.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.3"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ypCR Nodes</title>
        <description>Percentage of patients with no histologic evidence of cancer in axillary lymph nodes.</description>
        <time_frame>At the time of surgery approximately 24 to 28 weeks.</time_frame>
        <population>1 patient in Arm 1 was not analyzed due to inoperable, progressive disease. 2 patients in Arm 2 are missing data.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>ypCR Nodes</title>
          <description>Percentage of patients with no histologic evidence of cancer in axillary lymph nodes.</description>
          <population>1 patient in Arm 1 was not analyzed due to inoperable, progressive disease. 2 patients in Arm 2 are missing data.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.1"/>
                    <measurement group_id="O2" value="30.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Overall Response (cOR)(Complete and Partial) Assessed by MRI at the Completion of WP or Eribulin (Before AC)</title>
        <description>Percentage of patients with clinical complete response (no significant enhancement on MR images) or clinical partial response (at least 30% decrease in the maximal diameter of the tumor)</description>
        <time_frame>12 weeks after initiation of study therapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Overall Response (cOR)(Complete and Partial) Assessed by MRI at the Completion of WP or Eribulin (Before AC)</title>
          <description>Percentage of patients with clinical complete response (no significant enhancement on MR images) or clinical partial response (at least 30% decrease in the maximal diameter of the tumor)</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Complete Response (ycCR) Following Neoadjuvant Therapy Assessed by Physical Exam at the Completion of Neoadjuvant Chemotherapy</title>
        <description>The number of patients with clinical complete response.</description>
        <time_frame>At approximately 24 to 28 weeks from initiation of study therapy</time_frame>
        <population>1 patient in Arm 1 and 3 patients in Arm 2 are missing data. The N=18 for the paclitaxel group is because analysis was done on only patients with a palpable lesion at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Complete Response (ycCR) Following Neoadjuvant Therapy Assessed by Physical Exam at the Completion of Neoadjuvant Chemotherapy</title>
          <description>The number of patients with clinical complete response.</description>
          <population>1 patient in Arm 1 and 3 patients in Arm 2 are missing data. The N=18 for the paclitaxel group is because analysis was done on only patients with a palpable lesion at baseline.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Recurrence Free Interval (RFI): The Time to Occurrence of Inoperable Progressive Disease and Local, Regional, and Distant Recurrence.</title>
        <description>The percentage of patients free from recurrence at 24 months.</description>
        <time_frame>Assessed through 24 months from randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Recurrence Free Interval (RFI): The Time to Occurrence of Inoperable Progressive Disease and Local, Regional, and Distant Recurrence.</title>
          <description>The percentage of patients free from recurrence at 24 months.</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.6" lower_limit="57.3" upper_limit="94.4"/>
                    <measurement group_id="O2" value="80.7" lower_limit="59.6" upper_limit="91.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>2-year Overall Survival (OS): Death From Any Cause From Time of Randomization Through 2 Years After Randomization.</title>
        <description>Percentage of patients alive at 24 months.</description>
        <time_frame>Assessed through 24 months from randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>2-year Overall Survival (OS): Death From Any Cause From Time of Randomization Through 2 Years After Randomization.</title>
          <description>Percentage of patients alive at 24 months.</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.5" lower_limit="61.4" upper_limit="97.0"/>
                    <measurement group_id="O2" value="92.6" lower_limit="73.5" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events Experienced by Participants as a Measure of Toxicity.</title>
        <description>Total patients with at least 1 AE.</description>
        <time_frame>Assessed through 24 months from randomization</time_frame>
        <population>Please refer to the AE section for more detail.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: Paclitaxel Then AC</title>
            <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: Eribulin Then AC</title>
            <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events Experienced by Participants as a Measure of Toxicity.</title>
          <description>Total patients with at least 1 AE.</description>
          <population>Please refer to the AE section for more detail.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Emergent Adverse Events are those reported on or after the first administration and until 30 days after the last dose.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm 1: Paclitaxel Then AC</title>
          <description>Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Paclitaxel: 80 mg/m2 IV over 60 minutes weekly for 12 weeks&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
        </group>
        <group group_id="E2">
          <title>Arm 2: Eribulin Then AC</title>
          <description>Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles&#xD;
Eribulin: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles&#xD;
Doxorubicin: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles&#xD;
Cyclophosphamide: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (16.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Axillary pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </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" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nail discolouration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Diana Gosik</name_or_title>
      <organization>NSABP Foundation, Inc.</organization>
      <phone>412-339-5333</phone>
      <email>diana.gosik@nsabp.org</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/NCT01705691
org study id: NSABP FB-9
nct id: NCT01705691
lead sponsor: 
collaborator: 
has dmc: No
NSABP FB-9 is a Phase II, multi-center, randomized study of eribulin or weekly paclitaxel
      followed by doxorubicin and cyclophosphamide (AC) as neoadjuvant therapy for women with
      HER2-negative, operable and locally advanced breast cancer (stage IIb and III). Patients in
      the control arm will receive neoadjuvant weekly paclitaxel (WP) followed by AC. The primary
      aim of the study is to determine the pathologic complete response (ypCR) in breast and
      axillary lymph nodes following completion of neoadjuvant therapy. The secondary aims include
      determination of the ypCR in axillary nodes, clinical complete response (ycCR) rate after
      eribulin or paclitaxel and after completion of neoadjuvant chemotherapy, two-year
      recurrence-free interval, two-year overall survival, and toxicity of the neoadjuvant
      regimens.
Patients will be randomized to one of two neoadjuvant therapy regimens. Patients in Arm 1
      will receive WP 80 mg/m2 for 12 doses followed by standard AC every 21 days for 4 cycles.
      Patients in Arm 2 will receive 4 cycles of eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day
      cycle followed by standard AC every 21 days for 4 cycles. As soon as possible following
      recovery from chemotherapy, the patient will have either lumpectomy or mastectomy and
      axillary staging.

      In both arms, clinical response will be assessed by physical exam on day 1 of each study
      therapy cycle. MRI of the breast is required within 4 weeks prior to randomization and
      following completion of eribulin or WP (before starting AC). Following recovery from surgery,
      patients will receive radiation therapy and hormonal therapy as clinically indicated. Other
      postoperative therapies are prohibited.

      Patients will be randomized to the control arm (Arm 1) and to the investigational arm (Arm 2)
      in a 1:2 ratio. The sample size will be up to 50 patients with about 30 patients in Arm 2 and
      about half that number in Arm 1. Accrual is expected to occur over 15 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic Complete Response Rate (ypCR) Following Neoadjuvant Therapy in Breast and Axillary Lymph Nodes
time frame: At the time of surgery approximately 24 to 28 weeks.
description: Percentage of patients with no histologic evidence of cancer in breast and axillary lymph nodes.
measure: ypCR Nodes
time frame: At the time of surgery approximately 24 to 28 weeks.
description: Percentage of patients with no histologic evidence of cancer in axillary lymph nodes.
measure: Clinical Overall Response (cOR)(Complete and Partial) Assessed by MRI at the Completion of WP or Eribulin (Before AC)
time frame: 12 weeks after initiation of study therapy
description: Percentage of patients with clinical complete response (no significant enhancement on MR images) or clinical partial response (at least 30% decrease in the maximal diameter of the tumor)
measure: Clinical Complete Response (ycCR) Following Neoadjuvant Therapy Assessed by Physical Exam at the Completion of Neoadjuvant Chemotherapy
time frame: At approximately 24 to 28 weeks from initiation of study therapy
description: The number of patients with clinical complete response.
measure: Recurrence Free Interval (RFI): The Time to Occurrence of Inoperable Progressive Disease and Local, Regional, and Distant Recurrence.
time frame: Assessed through 24 months from randomization
description: The percentage of patients free from recurrence at 24 months.
measure: 2-year Overall Survival (OS): Death From Any Cause From Time of Randomization Through 2 Years After Randomization.
time frame: Assessed through 24 months from randomization
description: Percentage of patients alive at 24 months.
measure: Adverse Events Experienced by Participants as a Measure of Toxicity.
time frame: Assessed through 24 months from randomization
description: Total patients with at least 1 AE.
arm group label: Arm 1: Paclitaxel then AC
arm group type: Active Comparator
description: Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles
arm group label: Arm 2: Eribulin then AC
arm group type: Experimental
description: Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles
intervention type: Drug
intervention name: Paclitaxel
description: 80 mg/m2 IV over 60 minutes weekly for 12 weeks
arm group label: Arm 1: Paclitaxel then AC
intervention type: Drug
intervention name: Eribulin
description: 1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles
arm group label: Arm 2: Eribulin then AC
other name: eribulin mesylate
intervention type: Drug
intervention name: Doxorubicin
description: 60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles
arm group label: Arm 1: Paclitaxel then AC
arm group label: Arm 2: Eribulin then AC
intervention type: Drug
intervention name: Cyclophosphamide
description: 600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles
arm group label: Arm 1: Paclitaxel then AC
arm group label: Arm 2: Eribulin then AC
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Norman Wolmark, MD
role: Principal Investigator
affiliation: NSABP Foundation Inc
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Doxorubicin
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
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