<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/NCT02215876</url>
  </required_header>
  <id_info>
    <org_study_id>JS1405</org_study_id>
    <secondary_id>2013/01251</secondary_id>
    <nct_id>NCT02215876</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Eribulin Chemotherapy (ACE) in Operable HER2-negative Breast Cancer</brief_title>
  <official_title>A Phase II (Single Center) Study of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Eribulin Chemotherapy (ACE) in Operable HER2-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II, single institutional study, to evaluate a novel neo-adjuvant regimen in&#xD;
      patients with operable, HER2-negative, breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No patients recruited.&#xD;
  </why_stopped>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">March 2020</completion_date>
  <primary_completion_date type="Anticipated">August 2017</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>Pathologic Response Rate</measure>
    <time_frame>Estimated 6 months</time_frame>
    <description>To evaluate the pathologic complete response (pCR) rate following neoadjuvant treatment with four cycles of Doxorubicin and Cyclophosphamide (AC) and four cycles of Eribulin mesylate chemotherapy in HER2-negative operable breast cancer.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doxorubucin and Cyclophosphamide q2 or q3 weekly x 4 cycles plus Eribulin on days 1 and 8 of a 21 day cycle x 4 cycles</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Doxorubicin 60mg/m2 administered intravenously over 5 minutes on day 1 of a 14 of 21 days cycle IV for 4 cycles</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide 600mg/m2 administered intravenously over 60 minutes on day 1 of a 14 of 21 days cycle IV for 4 cycles</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eribulin</intervention_name>
    <description>Eribulin 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of a 21 day cycle for 4 cycles</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Written Informed Consent&#xD;
&#xD;
          2. Target Population&#xD;
&#xD;
               1. Histologically confirmed primary invasive adenocarcinoma of the breast.&#xD;
&#xD;
               2. Patients with operable, T2-4, N0-3, M0, T1N1 breast cancer (stage IIA, IIB, IIIA,&#xD;
                  IIIB and IIIC) with minimum tumor size of 2 cm&#xD;
&#xD;
               3. Tumors must be HER-2/neu expression negative, as determined by local hospital&#xD;
                  laboratory (IHC ≤ 2+ or FISH negative).&#xD;
&#xD;
               4. No prior treatment (irradiation, chemotherapy, hormonal, immunotherapy or&#xD;
                  investigational, etc.) for breast cancer excluding therapy for DCIS. Subjects&#xD;
                  receiving hormone replacement therapy (HRT) are eligible if this therapy is&#xD;
                  discontinued at least 2 weeks before starting study therapy.&#xD;
&#xD;
               5. Subjects who received radiotherapy for DCIS may enroll.&#xD;
&#xD;
               6. Disease free of prior malignancy for ≥ 5 years with the exception of curatively&#xD;
                  treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.&#xD;
&#xD;
               7. ECOG PS of 0 or 1.&#xD;
&#xD;
               8. Accessible for treatment and follow-up.&#xD;
&#xD;
               9. Baseline cardiac echocardiogram scan with LVEF of ≥ 50%.&#xD;
&#xD;
              10. Adequate recovery from recent surgery. At least one week must have elapsed from&#xD;
                  minor surgery (placement of venous access device or fine needle aspiration) and&#xD;
                  at least 4 weeks from major surgery.&#xD;
&#xD;
          3. Laboratory Parameters&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1500/mm3&#xD;
&#xD;
               2. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN).&#xD;
&#xD;
               3. AST or ALT ≤ 2.5 times the upper limit of normal (ULN).&#xD;
&#xD;
               4. Platelets ≥ 100,000/ mm3.&#xD;
&#xD;
               5. Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance &gt; 60 mL/min&#xD;
                  (measured or calculated by Cockcroft-Gault method).&#xD;
&#xD;
               6. Normal PTT and either INR or PT &lt; 1.5 x ULN.&#xD;
&#xD;
          4. Age and Sex Women, at least 21 years of age. a) Women of childbearing potential&#xD;
             (WOCBP) must be using an adequate method of contraception to avoid pregnancy&#xD;
             throughout the study and for up to 8 weeks after the last dose of chemotherapy in such&#xD;
             a manner that the risk of pregnancy is minimized.&#xD;
&#xD;
        WOCBP include any woman who has experienced menarche and who has not undergone successful&#xD;
        surgical sterilization (hysterectomy, bilateral tubal ligation,or bilateral oophorectomy)&#xD;
        or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on&#xD;
        hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH]&#xD;
        level &gt; 35 mIU/mL). Even women who are using oral contraceptives, other hormonal&#xD;
        contraceptives (vaginal products, skin patches, or implanted or injectable products), or&#xD;
        mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms,&#xD;
        spermicides) to prevent pregnancy, or are practicing abstinence or whose partner is sterile&#xD;
        (vasectomy) should be considered to be of childbearing potential.&#xD;
&#xD;
        WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or&#xD;
        equivalent units of HCG) within 72 hours before the first dose of investigational product.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Sex and Reproductive Status&#xD;
&#xD;
               1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy&#xD;
                  for the entire study period and for up to 8 weeks after the last dose of&#xD;
                  chemotherapy.&#xD;
&#xD;
               2. Women who are pregnant (including positive pregnancy test at enrollment or prior&#xD;
                  to study drug administration) or breastfeeding.&#xD;
&#xD;
          2. Target Disease Exceptions&#xD;
&#xD;
               1. Evidence of metastatic breast cancer following a standard tumor staging work-up.&#xD;
&#xD;
               2. Evidence of inflammatory breast cancer.&#xD;
&#xD;
               3. Evidence of baseline sensory or motor neuropathy.&#xD;
&#xD;
          3. Medical History and Concurrent Diseases&#xD;
&#xD;
               1. Known human immunodeficiency viral (HIV) infection.&#xD;
&#xD;
               2. Serious intercurrent infections or non-malignant medical illnesses that are&#xD;
                  uncontrolled or the control of which may be jeopardized by this therapy.&#xD;
&#xD;
               3. Psychiatric disorders or other conditions rendering the subject incapable of&#xD;
                  complying with the requirements of the protocol.&#xD;
&#xD;
               4. Clinically significant history of cardiovascular disease (history of unstable&#xD;
                  angina, congestive heart failure, uncontrolled hypertension, myocardial&#xD;
                  infarction or valvular heart disease).&#xD;
&#xD;
               5. Subjects unfit for breast and/or axillary surgery (complete fixation of tumor,&#xD;
                  skin infiltration, erythema of the breast, and/or ulceration).&#xD;
&#xD;
               6. Current participation in another drug trial.&#xD;
&#xD;
               7. Subjects who received prior anthracycline therapy.&#xD;
&#xD;
               8. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated)&#xD;
                  for treatment of either a psychiatric or physical illness (e.g., infectious&#xD;
                  disease) must not be enrolled into this study.&#xD;
&#xD;
             Eligibility criteria for this study have been carefully considered to ensure the&#xD;
             safety of the study subjects and to ensure that the results of the study can be used.&#xD;
             It is imperative that subjects fully meet all eligibility criteria.&#xD;
&#xD;
          4. Allergies and Adverse Drug Reactions&#xD;
&#xD;
             a) Known allergy to any of the study drugs&#xD;
&#xD;
          5. Prohibited Therapies and/or Medications a) Other concurrent anti-tumor, chemotherapy,&#xD;
             hormonal therapy, immunotherapy regimens or radiation therapy, standard or&#xD;
             investigational.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Akhil Chopra</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins Singapore</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>308433</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>April 13, 2016</last_update_submitted>
  <last_update_submitted_qc>April 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Her 2-negative breast cancer</keyword>
  <keyword>neoadjuvant doxorubicin/cyclophosphamide followed by Eribulin chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02215876
org study id: JS1405
secondary id: 2013/01251
nct id: NCT02215876
lead sponsor: 
has dmc: Yes
This is a phase II, single institutional study, to evaluate a novel neo-adjuvant regimen in
      patients with operable, HER2-negative, breast cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic Response Rate
time frame: Estimated 6 months
description: To evaluate the pathologic complete response (pCR) rate following neoadjuvant treatment with four cycles of Doxorubicin and Cyclophosphamide (AC) and four cycles of Eribulin mesylate chemotherapy in HER2-negative operable breast cancer.
arm group label: Single Arm
arm group type: Experimental
description: Doxorubucin and Cyclophosphamide q2 or q3 weekly x 4 cycles plus Eribulin on days 1 and 8 of a 21 day cycle x 4 cycles
intervention type: Drug
intervention name: Doxorubicin
description: Doxorubicin 60mg/m2 administered intravenously over 5 minutes on day 1 of a 14 of 21 days cycle IV for 4 cycles
arm group label: Single Arm
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide 600mg/m2 administered intravenously over 60 minutes on day 1 of a 14 of 21 days cycle IV for 4 cycles
arm group label: Single Arm
intervention type: Drug
intervention name: Eribulin
description: Eribulin 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of a 21 day cycle for 4 cycles
arm group label: Single Arm
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 100 Years
healthy volunteers: No
last name: Akhil Chopra
role: Principal Investigator
affiliation: Johns Hopkins Singapore
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Cyclophosphamide
mesh term: Doxorubicin