<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/NCT02980965</url>
  </required_header>
  <id_info>
    <org_study_id>NCET-trial</org_study_id>
    <nct_id>NCT02980965</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Chemo-endocrine Therapy Versus Chemotherapy Alone in ER-positive, HER2-negative Breast Cancer</brief_title>
  <official_title>A Randomized Controlled Study to Evaluate the Efficacy and Safety of Endocrine Therapy Plus Chemotherapy Versus Chemotherapy Alone as the Neoadjuvant Therapy in the Treatment of ER-positive, HER2-negative Breast Cancer (IIa-IIIc)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was an open-label, randomized controlled trial that aims to compare the efficacy and&#xD;
      safety of the concurrent neoadjuvant chemotherapy with endocrine therapy and neoadjuvant&#xD;
      chemotherapy alone in ER-positive, HER2-negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Data showed that concurrent neoadjuvant chemotherapy with endocrine therapy was a effective&#xD;
      option for ER-positive, HER2-negative breast cancer patients. However this is still a&#xD;
      controversial issue. The present study is an open-label randomized controlled clinical trial&#xD;
      that aims to investigate the efficacy of concurrent NCT with endocrine therapy (AI with or&#xD;
      without GnRH-a) in patients with ER-positive, HER2-negative breast carcinoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>objective response rate (ORR)</measure>
    <time_frame>4 years</time_frame>
    <description>the proportion of patients achieving clinical complete response and partial response in the breast based on magnetic resonance imaging</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ki67 proliferation marker changes</measure>
    <time_frame>4 years</time_frame>
    <description>Absolute Ki67 change as well as geometric mean percentage change in Ki67 positivity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pathologic complete response (pCR)</measure>
    <time_frame>4 years</time_frame>
    <description>Disappearance of residual invasive disease (residual ductal carcinoma in situ allowed) in breast and the absence of positive lymph nodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pathological response rate</measure>
    <time_frame>4 years</time_frame>
    <description>The proportion of patients achieving pathological response based on Miller-Payne grading system</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (DFS)</measure>
    <time_frame>6 years</time_frame>
    <description>The interval between the date of randomization to disease progression during treatment, any recurrence, contralateral breast cancer, the appearance of a second primary cancer, or death not due to cancer, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Serious Treatment-Emergent Adverse Events(grade 3 or 4)</measure>
    <time_frame>4 years</time_frame>
    <description>Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">249</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>neoadjuvant chemo-endocrine therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the experimental arm, patients received concurrent chemotherapy (fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles) with endocrine therapy (letrozole with or without leuprorelin) as a neoadjuvant treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>neoadjuvant chemotherapy alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the control group, patients received neoadjuvant chemotherapy alone (fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>letrozole, leuprorelin, fluorouracil, epirubicin, cyclophosphamide, docetaxel</intervention_name>
    <description>Postmenopausal patients were treated with letrozole 2.5mg/day p.o until complement of neoadjuvant chemotherapy before surgery, while premenopausal ones received letrozole 2.5mg/day p.o and a subcutaneous injection of the GnRH-a, leuprorelin, as concomitant treatment with neoadjuvant chemotherapy (fluorouracil 600mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 80mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles), letrozole was delivered after 1 week of first dose of leuprorelin injection.</description>
    <arm_group_label>neoadjuvant chemo-endocrine therapy</arm_group_label>
    <other_name>GnRH-a, ENANTONE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fluorouracil, epirubicin, cyclophosphamide, docetaxel</intervention_name>
    <description>Patients received fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles.</description>
    <arm_group_label>neoadjuvant chemotherapy alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Estrogen receptor-positive and HER2-negative breast cancer patients, with histological&#xD;
             stage of IIa-IIIc.&#xD;
&#xD;
          2. Without previous chemotherapy or endocrine therapy.&#xD;
&#xD;
          3. ECOG scores of 0-2 points&#xD;
&#xD;
          4. With measurable and evaluable breast tumor pathologically confirmed as invasive ductal&#xD;
             carcinoma&#xD;
&#xD;
          5. Age: 18-70 years&#xD;
&#xD;
          6. Lateral breast cancer&#xD;
&#xD;
          7. Normal or acceptable kidney, liver, cardiovascular, and bone marrow functions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant women or nursing mothers&#xD;
&#xD;
          2. With distant metastasis&#xD;
&#xD;
          3. With a history of malignant tumor or complicated with other malignant tumors in&#xD;
             addition to breast cancer, except for non-melanoma skin cancer, in situ cervical&#xD;
             cancer or other cured malignant tumor without the basis of recurrence for at least&#xD;
             five years&#xD;
&#xD;
          4. With mental illness or other conditions affecting the patient compliance&#xD;
&#xD;
          5. With other serious diseases or medical conditions:&#xD;
&#xD;
               1. Congestive heart failure or unstable angina pectoris, myocardial infarction&#xD;
                  within 6 months before the enrollment, uncontrolled hypertension and uncontrolled&#xD;
                  high-risk arrhythmia considered by the investigator&#xD;
&#xD;
               2. Obvious neurological or psychiatric disorders, including psychosis, epileptic&#xD;
                  dementia and other diseases may affect the understanding and sign of the informed&#xD;
                  consent for&#xD;
&#xD;
               3. Uncontrolled acute infection&#xD;
&#xD;
          6. Concurrent use of other investigational drugs; or participating in other clinical&#xD;
             trials involving investigational drugs within 30 days before this study&#xD;
&#xD;
          7. With allergic constitution and any known or suspected drug allergy&#xD;
&#xD;
          8. Not suitable for the trial considered by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhi-Min Shao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Hospital/ Institute, Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Hospital/ Institute, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>November 26, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>November 8, 2017</last_update_submitted>
  <last_update_submitted_qc>November 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Zhimin Shao</investigator_full_name>
    <investigator_title>Director of Department of Surgical Oncology,Cancer Hospital &amp; Institute</investigator_title>
  </responsible_party>
  <keyword>breast cancer</keyword>
  <keyword>neoadjuvant chemotherapy</keyword>
  <keyword>endocrine therapy</keyword>
  <keyword>concurrent</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>Docetaxel</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Leuprolide</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/NCT02980965
org study id: NCET-trial
nct id: NCT02980965
lead sponsor: 
has dmc: Yes
This was an open-label, randomized controlled trial that aims to compare the efficacy and
      safety of the concurrent neoadjuvant chemotherapy with endocrine therapy and neoadjuvant
      chemotherapy alone in ER-positive, HER2-negative breast cancer.
Data showed that concurrent neoadjuvant chemotherapy with endocrine therapy was a effective
      option for ER-positive, HER2-negative breast cancer patients. However this is still a
      controversial issue. The present study is an open-label randomized controlled clinical trial
      that aims to investigate the efficacy of concurrent NCT with endocrine therapy (AI with or
      without GnRH-a) in patients with ER-positive, HER2-negative breast carcinoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: objective response rate (ORR)
time frame: 4 years
description: the proportion of patients achieving clinical complete response and partial response in the breast based on magnetic resonance imaging
measure: Ki67 proliferation marker changes
time frame: 4 years
description: Absolute Ki67 change as well as geometric mean percentage change in Ki67 positivity
measure: pathologic complete response (pCR)
time frame: 4 years
description: Disappearance of residual invasive disease (residual ductal carcinoma in situ allowed) in breast and the absence of positive lymph nodes
measure: pathological response rate
time frame: 4 years
description: The proportion of patients achieving pathological response based on Miller-Payne grading system
measure: Progression-free survival (DFS)
time frame: 6 years
description: The interval between the date of randomization to disease progression during treatment, any recurrence, contralateral breast cancer, the appearance of a second primary cancer, or death not due to cancer, whichever occurred first.
measure: Incidence of Serious Treatment-Emergent Adverse Events(grade 3 or 4)
time frame: 4 years
description: Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
arm group label: neoadjuvant chemo-endocrine therapy
arm group type: Experimental
description: In the experimental arm, patients received concurrent chemotherapy (fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles) with endocrine therapy (letrozole with or without leuprorelin) as a neoadjuvant treatment
arm group label: neoadjuvant chemotherapy alone
arm group type: Active Comparator
description: In the control group, patients received neoadjuvant chemotherapy alone (fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles)
intervention type: Drug
intervention name: letrozole, leuprorelin, fluorouracil, epirubicin, cyclophosphamide, docetaxel
description: Postmenopausal patients were treated with letrozole 2.5mg/day p.o until complement of neoadjuvant chemotherapy before surgery, while premenopausal ones received letrozole 2.5mg/day p.o and a subcutaneous injection of the GnRH-a, leuprorelin, as concomitant treatment with neoadjuvant chemotherapy (fluorouracil 600mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 80mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles), letrozole was delivered after 1 week of first dose of leuprorelin injection.
arm group label: neoadjuvant chemo-endocrine therapy
other name: GnRH-a, ENANTONE
intervention type: Drug
intervention name: fluorouracil, epirubicin, cyclophosphamide, docetaxel
description: Patients received fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles.
arm group label: neoadjuvant chemotherapy alone
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Zhi-Min Shao, MD
role: Principal Investigator
affiliation: Cancer Hospital/ Institute, Fudan University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Zhimin Shao
investigator title: Director of Department of Surgical Oncology,Cancer Hospital & Institute
mesh term: Breast Neoplasms
mesh term: Cyclophosphamide
mesh term: Docetaxel
mesh term: Fluorouracil
mesh term: Letrozole
mesh term: Epirubicin
mesh term: Leuprolide