<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/NCT01712893</url>
  </required_header>
  <id_info>
    <org_study_id>CD trial</org_study_id>
    <nct_id>NCT01712893</nct_id>
  </id_info>
  <brief_title>Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa in Treating ER+,Premenopausal Breast Cancer</brief_title>
  <official_title>A Phase III,Randomized,Open Label Study Comparing Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa up to 2-3 Years for ≤ 45 Year Old Pre-menopausal Hormone Receptor-positive Breast Cancer</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>
      The present study is a randomized open-label -phase III study that aims to compare the&#xD;
      efficacy and safety of the adjuvant chemotherapy with simultaneous or sequential application&#xD;
      of Zoladex up to 2-3 years for ≤ 45 year old premenopausal hormone receptor-positive breast&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Data showed that ovarian suppression therapy may protect the ovarian function in&#xD;
      premenopausal patients received chemotherapy for breast cancer. However this is still a&#xD;
      controversial issue. Sequential use of GnRHa (Zoladex) as ovarian suppression treatment after&#xD;
      chemotherapy has been established as an effective endocrine therapy for ER positive&#xD;
      premenopausal breast cancer. The present study is a randomized open-label phase III study&#xD;
      that aims to observe the efficacy and safety of the adjuvant chemotherapy with simultaneous&#xD;
      combination of Zoladex up to 2-3years and chemotherapy compared with the sequential schedule&#xD;
      in ≤ 45 year old premenopausal hormone receptor-positive breast cancer patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2009</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">August 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>Resumption of menstruation</measure>
    <time_frame>1 year</time_frame>
    <description>the Resumption that patients recover the natural menstrual or serum E2, FSH, LH return to the premenopausal range within 1 year after stopping Zoladex</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RFS</measure>
    <time_frame>5years</time_frame>
    <description>Relapse free survival (RFS): RFS related events ware defined as local-regional recurrence, distant metastasis or death, whichever occurred first.during follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>5 years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other adverse events</measure>
    <time_frame>5years</time_frame>
    <description>Other adverse events (Gynecological events, blood lipids, thrombosis, cardiovascular diseases, and etc.)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">216</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Zoladex combined with chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After signing informed consent, patients will be screened, eligible patients were randomly divided into 2 groups, the test group should use Zoladex 3.6mg once a month up to 2-3 years combined with chemotherapy,all patients will receive Tamoxifen after chemotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Zoladex after chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After signing informed consent, patients will be screened, eligible patients were randomly divided into 2 groups, the control group should use Zoladex 3.6mg once a month up to 2-3 years after chemotherapy,all patients will receive Tamoxifen after chemotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zoladex</intervention_name>
    <description>Eligible patients were randomly divided into 2 groups, the intervention group should use Zoladex 3.6mg once a month up to 2-3 years combined with chemotherapy,and the control group should use chemotherapy alone followed by Zoladex</description>
    <arm_group_label>Zoladex after chemotherapy</arm_group_label>
    <arm_group_label>Zoladex combined with chemotherapy</arm_group_label>
    <other_name>Zoladex = GnRHa,Goserelin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. female&#xD;
&#xD;
          2. Primary invasive breast cancer pathologically approved by core needle or open biopsy&#xD;
&#xD;
          3. Patients must have undergone standard surgery for primary breast cancer as shown in&#xD;
             the following:&#xD;
&#xD;
               -  mastectomy&#xD;
&#xD;
               -  breast conservation surgery followed by whole breast radiation&#xD;
&#xD;
               -  axillary dissection or sentinel node biopsy&#xD;
&#xD;
          4. Need adjuvant chemotherapy after surgery&#xD;
&#xD;
          5. Patients taking neo-chemotherapy are eligible&#xD;
&#xD;
          6. Patients with synchronous bilateral cancers are eligible on the condition that If one&#xD;
             side is IDC and the other side is DCIS, the IDC side should be of the ER and/or PR&#xD;
             positive phenotype and IF two sides are both IDC, they must be ER and/or PR positive&#xD;
             phenotype at the same time&#xD;
&#xD;
          7. Hormone receptor positive (≥＋) is defined as detecting ER or PR expression at any time&#xD;
             is eligible. The situation of only PR positive and ER negative is eligible, too&#xD;
&#xD;
          8. Based on the study objective, all patients are required to be premenopausal as defined&#xD;
             by&#xD;
&#xD;
               -  menstruating actively&#xD;
&#xD;
               -  less than 6 months since last menstrual period (LMP), or patients younger than 40&#xD;
                  years of age who became amenorrheic not more than 1 year if the serum free E2、FSH&#xD;
                  and LH level was premenopausal (according to the reference value of local&#xD;
                  center).&#xD;
&#xD;
               -  had previous hysterectomy with one or both ovaries left intact are eligible if&#xD;
                  the serum free E2、FSH and LH level are premenopausal (according to the reference&#xD;
                  value of local center).&#xD;
&#xD;
          9. patients must have an ECOG performance status of 0 or 1 (0-fully active, able to carry&#xD;
             on all pre-disease performance without restriction, 1-restricted in physical strenuous&#xD;
             actively but ambulatory)&#xD;
&#xD;
         10. leucocyte count must be ≥ 3.0*10^9/L and platelet count must be ≥ 100*10^9/L&#xD;
&#xD;
         11. AST/SGOT or ALT/AGPT must be &lt; 3 times the ULN&#xD;
&#xD;
         12. serum creatinine must be &lt; 2 times the ULN&#xD;
&#xD;
         13. pregnancy testing is negative and are willing to do contraception during the treatment&#xD;
             period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patients with metastatic malignant tumor&#xD;
&#xD;
          2. previous history of asynchronous bilateral breast cancer&#xD;
&#xD;
          3. any previous malignancy in the past 5 years, except for those treated with curative&#xD;
             intent, such as carcinoma in situ of the cervix, squamous carcinoma of the skin or&#xD;
             basal cell carcinoma of the skin&#xD;
&#xD;
          4. any non-malignant systemic disease which interfere long time follow up&#xD;
&#xD;
          5. history of medical ovarian ablation therapy&#xD;
&#xD;
          6. severe live dysfunction, Child-Pugh is grade C&#xD;
&#xD;
          7. Severe renal dysfunction&#xD;
&#xD;
          8. Occult breast cancer&#xD;
&#xD;
          9. severe heart dysfunction, heart functional classification is above Class III&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhi-Min Shao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>FUSCC</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>August 2017</verification_date>
  <study_first_submitted>October 21, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <last_update_submitted>August 24, 2017</last_update_submitted>
  <last_update_submitted_qc>August 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 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>adjuvant therapy</keyword>
  <keyword>Ovarian suppression</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>Goserelin</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/NCT01712893
org study id: CD trial
nct id: NCT01712893
lead sponsor: 
has dmc: Yes
The present study is a randomized open-label -phase III study that aims to compare the
      efficacy and safety of the adjuvant chemotherapy with simultaneous or sequential application
      of Zoladex up to 2-3 years for ≤ 45 year old premenopausal hormone receptor-positive breast
      cancer.
Data showed that ovarian suppression therapy may protect the ovarian function in
      premenopausal patients received chemotherapy for breast cancer. However this is still a
      controversial issue. Sequential use of GnRHa (Zoladex) as ovarian suppression treatment after
      chemotherapy has been established as an effective endocrine therapy for ER positive
      premenopausal breast cancer. The present study is a randomized open-label phase III study
      that aims to observe the efficacy and safety of the adjuvant chemotherapy with simultaneous
      combination of Zoladex up to 2-3years and chemotherapy compared with the sequential schedule
      in ≤ 45 year old premenopausal hormone receptor-positive breast cancer patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Resumption of menstruation
time frame: 1 year
description: the Resumption that patients recover the natural menstrual or serum E2, FSH, LH return to the premenopausal range within 1 year after stopping Zoladex
measure: RFS
time frame: 5years
description: Relapse free survival (RFS): RFS related events ware defined as local-regional recurrence, distant metastasis or death, whichever occurred first.during follow up
measure: OS
time frame: 5 years
description: Overall survival
measure: Other adverse events
time frame: 5years
description: Other adverse events (Gynecological events, blood lipids, thrombosis, cardiovascular diseases, and etc.)
arm group label: Zoladex combined with chemotherapy
arm group type: Experimental
description: After signing informed consent, patients will be screened, eligible patients were randomly divided into 2 groups, the test group should use Zoladex 3.6mg once a month up to 2-3 years combined with chemotherapy,all patients will receive Tamoxifen after chemotherapy
arm group label: Zoladex after chemotherapy
arm group type: Active Comparator
description: After signing informed consent, patients will be screened, eligible patients were randomly divided into 2 groups, the control group should use Zoladex 3.6mg once a month up to 2-3 years after chemotherapy,all patients will receive Tamoxifen after chemotherapy
intervention type: Drug
intervention name: Zoladex
description: Eligible patients were randomly divided into 2 groups, the intervention group should use Zoladex 3.6mg once a month up to 2-3 years combined with chemotherapy,and the control group should use chemotherapy alone followed by Zoladex
arm group label: Zoladex after chemotherapy
arm group label: Zoladex combined with chemotherapy
other name: Zoladex = GnRHa,Goserelin
criteria: 
gender: Female
minimum age: N/A
maximum age: 45 Years
healthy volunteers: No
last name: Zhi-Min Shao, MD
role: Principal Investigator
affiliation: 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: Goserelin