<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/NCT02221999</url>
  </required_header>
  <id_info>
    <org_study_id>RenJiH-BC-002</org_study_id>
    <nct_id>NCT02221999</nct_id>
  </id_info>
  <brief_title>Weekly Paclitaxel and Cisplatin to Treat Hormone Receptor Positive and Triple Negative Breast Cancer Patients</brief_title>
  <acronym>SHPD002</acronym>
  <official_title>A Prospective, Randomized, Open-label Comparison of Preoperative Weekly Paclitaxel and Cisplatin With or Without Endocrine Therapy in Patients With Operable Hormone Receptor Positive and Triple Negative Locally Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RenJi Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that paclitaxel combined with cisplatin in a weekly-based&#xD;
      regimen as neoadjuvant chemotherapy is effective and tolerable for locally advanced breast&#xD;
      cancer.&#xD;
&#xD;
      In patients with some sub-type advanced breast cancer, neo-adjuvant chemotherapy combined&#xD;
      with endocrine therapy may improve the pathological remission rate.&#xD;
&#xD;
      Premenopausal patients with triple negative breast caner and hormonal receptor positve breast&#xD;
      cancer patients will be randominzed to have neoadjuvant chemotherapy combined with endocrine&#xD;
      therapy or not.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this trial, patients with ER and or PR positive breast cancer will be separately&#xD;
      randomized to have chemotherapy or chemotherapy combined with endocrine therapy according to&#xD;
      their menstrual status. Letrozole for the postmenopausal women and ovarian function&#xD;
      suppression for the premenopausal women. Patients with triple negative breast cancer will be&#xD;
      randomized to have neoadjuvant chemotherapy combined with ovarian function suppression if she&#xD;
      is premenopausal. Postermenopausal patients with triple negative breast caner will only have&#xD;
      neoadjuvant chemotherapy.&#xD;
&#xD;
      Patients with Her2 overexpression can obtain anti-Her2 target therapy. This study has been&#xD;
      amended to a 1:2 ratio to control and neoadjuvant chemotherapy combination of endocrine&#xD;
      therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 2013</start_date>
  <completion_date type="Anticipated">January 2029</completion_date>
  <primary_completion_date type="Actual">January 2019</primary_completion_date>
  <phase>Phase 2/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>pathological complete remission rate</measure>
    <time_frame>after 4 months preoperative treatment</time_frame>
    <description>Pathological complete remission is defined as no invasive cancer in breast and axillary nodes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Drug Related Treatment Adverse Events</measure>
    <time_frame>4 months during neoadjuvant therapy</time_frame>
    <description>Adverse events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical and imaging response</measure>
    <time_frame>4 months during treatment</time_frame>
    <description>To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease free survival (DFS)</measure>
    <time_frame>5 years</time_frame>
    <description>DFS is defined as the time in months from randomization until first occurrence of locoregional recurrence, distant metastasis, contralateral breast cancer, second primary tumor, or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>regional recurrence free survival (RRFS)</measure>
    <time_frame>5 years</time_frame>
    <description>RRFS is defined as the time period between registration and first event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>local recurrence free survival (LRFS)</measure>
    <time_frame>5 years</time_frame>
    <description>LRFS is defined as the time period between registration and first event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>5 years</time_frame>
    <description>OS is defined as the time period between registration and first event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>distant-disease- free survival (DDFS)</measure>
    <time_frame>5 years</time_frame>
    <description>DDFS is defined as the time period between registration and first event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of tumor remission （RTR）</measure>
    <time_frame>after 2 cycles and 4 cycles during neoadjuvant therapy</time_frame>
    <description>RTR is defined as the proportion of tumor remission per unit time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum markers</measure>
    <time_frame>Pre-treatment and/or surgical</time_frame>
    <description>Changes in the angiogenic serum markers(mirRNA, lncRNA, cirRNA), measured at diagnosis and surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>molecular markers</measure>
    <time_frame>Pre-treatment and/or surgical</time_frame>
    <description>Pre-treatment and surgical expression of molecular markers （LHRHa receptor, EGFR，PD-L1)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Tubular Breast Cancer</condition>
  <condition>Mucinous Breast Cancer</condition>
  <condition>Invasive Ductal Breast Cancer</condition>
  <condition>Inflammatory Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Chemotherapy only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Paclitaxel injection 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle；Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle； for 4 cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GnRHa</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Gonadotropin-releasing hormone agonist （GnRHa）11.25 mg every 3 months or 3.6mg every month subcutaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Letrozole 2.5mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <arm_group_label>Chemotherapy only</arm_group_label>
    <arm_group_label>GnRHa</arm_group_label>
    <arm_group_label>letrozole</arm_group_label>
    <other_name>Taxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <arm_group_label>Chemotherapy only</arm_group_label>
    <arm_group_label>GnRHa</arm_group_label>
    <arm_group_label>letrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gonadotropin-releasing hormone agonist</intervention_name>
    <description>Goserelin 3.6 mg q28d or Leuprolide 11.25 mg q3m</description>
    <arm_group_label>GnRHa</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <arm_group_label>letrozole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women aged ≥18years and ≤70 years;&#xD;
&#xD;
          2. At least on measurable disease according to the Response Evaluation Criteria in Solid&#xD;
             Tumors (RECIST). Histologically confirmed invasive breast cancer, tumor size ≥2 cm,&#xD;
             T2-4 N0-3M0;&#xD;
&#xD;
          3. ER/PR/HER-2 and Ki-67 status detected on core biopsy. ER and/or PR positive was&#xD;
             defined as &gt;1% stained cells.HER2-positive is defined as immuno-histochemistry (IHC)&#xD;
             3+ or the ratio of HER2 gene signals to chromosome 17 signals &gt;2.0 or HER2 gene copy&#xD;
             &gt;6.0.&#xD;
&#xD;
          4. No prior systemic or loco-regional treatment of breast cancer;&#xD;
&#xD;
          5. Adequate bone marrow function:WBC≥4.0×109/L, Absolute neutrophil count（ANC）≥1.5×109/L,&#xD;
             Platelets（PLT）≥100×109/L, Hemoglobin（Hb）≥90g/L;aspartate aminotransferase(AST),Alanine&#xD;
             aminotransferase (ALT)≤1.5 upper normal limit (UNL), creatinine≤1.5 UNL,&#xD;
             bilirubin≤1.5UNL;&#xD;
&#xD;
          6. No obvious main organs dysfunction.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unwilling or unable to use an acceptable method of contraception in 8 weeks (including&#xD;
             8 weeks) after final dose of test drug;&#xD;
&#xD;
          2. Patient is pregnant or breast feeding;&#xD;
&#xD;
          3. Inflammatory breast cancer and metastatic breast cancer;&#xD;
&#xD;
          4. Any evidence of sense or motor nerve disorders;&#xD;
&#xD;
          5. Patients with medical conditions taht indicate intolerant to neoadjuvant therapy,&#xD;
             including uncontrolled cardiovascular disease, severe infection;&#xD;
&#xD;
          6. Any concurrent malignancy other than breast cancer;&#xD;
&#xD;
          7. Know severe hypersensitivity to any drugs in this study.&#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>Jinsong Lu</last_name>
    <role>Principal Investigator</role>
    <affiliation>RenJi Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Thyroid and Breast Gland Surgery,Shenzhen Longgang Central Hospital</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HanDan Central Hospital</name>
      <address>
        <city>Handan</city>
        <state>Hebei</state>
        <zip>056001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of University of South China</name>
      <address>
        <city>Hengyang</city>
        <state>Hunan</state>
        <zip>421001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Thyroid and Breast Surgery, The Affiliated Hospital of Inner Mongolia Medical Collage</name>
      <address>
        <city>Hohhot</city>
        <state>Inner Mongolia</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The second people's hospital of Kunshan city</name>
      <address>
        <city>Kunshan</city>
        <state>Jiangsu</state>
        <zip>215300</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Medical Oncology, General Hospital of Ningxia Medical University</name>
      <address>
        <city>Yinchuan</city>
        <state>Ningxia</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Jiaotong University School of Medicine, Renji Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yueyang hospital of integrated traditional Chinese and Western medine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200437</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Armed Police Corps Hospital of Shanghai</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>201103</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhoushan hospital</name>
      <address>
        <city>Zhoushan</city>
        <state>Zhejiang</state>
        <zip>316021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>RenJi Hospital</investigator_affiliation>
    <investigator_full_name>Jinsong Lu</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Inflammatory Breast Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ductal, Breast</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Hormones</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/NCT02221999
org study id: RenJiH-BC-002
nct id: NCT02221999
lead sponsor: 
has dmc: Yes
The investigators hypothesize that paclitaxel combined with cisplatin in a weekly-based
      regimen as neoadjuvant chemotherapy is effective and tolerable for locally advanced breast
      cancer.

      In patients with some sub-type advanced breast cancer, neo-adjuvant chemotherapy combined
      with endocrine therapy may improve the pathological remission rate.

      Premenopausal patients with triple negative breast caner and hormonal receptor positve breast
      cancer patients will be randominzed to have neoadjuvant chemotherapy combined with endocrine
      therapy or not.
In this trial, patients with ER and or PR positive breast cancer will be separately
      randomized to have chemotherapy or chemotherapy combined with endocrine therapy according to
      their menstrual status. Letrozole for the postmenopausal women and ovarian function
      suppression for the premenopausal women. Patients with triple negative breast cancer will be
      randomized to have neoadjuvant chemotherapy combined with ovarian function suppression if she
      is premenopausal. Postermenopausal patients with triple negative breast caner will only have
      neoadjuvant chemotherapy.

      Patients with Her2 overexpression can obtain anti-Her2 target therapy. This study has been
      amended to a 1:2 ratio to control and neoadjuvant chemotherapy combination of endocrine
      therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pathological complete remission rate
time frame: after 4 months preoperative treatment
description: Pathological complete remission is defined as no invasive cancer in breast and axillary nodes.
measure: Number of Participants With Drug Related Treatment Adverse Events
time frame: 4 months during neoadjuvant therapy
description: Adverse events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state.
measure: Clinical and imaging response
time frame: 4 months during treatment
description: To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment
measure: disease free survival (DFS)
time frame: 5 years
description: DFS is defined as the time in months from randomization until first occurrence of locoregional recurrence, distant metastasis, contralateral breast cancer, second primary tumor, or death from any cause.
measure: regional recurrence free survival (RRFS)
time frame: 5 years
description: RRFS is defined as the time period between registration and first event
measure: local recurrence free survival (LRFS)
time frame: 5 years
description: LRFS is defined as the time period between registration and first event
measure: overall survival (OS)
time frame: 5 years
description: OS is defined as the time period between registration and first event
measure: distant-disease- free survival (DDFS)
time frame: 5 years
description: DDFS is defined as the time period between registration and first event
measure: rate of tumor remission （RTR）
time frame: after 2 cycles and 4 cycles during neoadjuvant therapy
description: RTR is defined as the proportion of tumor remission per unit time
measure: serum markers
time frame: Pre-treatment and/or surgical
description: Changes in the angiogenic serum markers(mirRNA, lncRNA, cirRNA), measured at diagnosis and surgery
measure: molecular markers
time frame: Pre-treatment and/or surgical
description: Pre-treatment and surgical expression of molecular markers （LHRHa receptor, EGFR，PD-L1)
arm group label: Chemotherapy only
arm group type: Active Comparator
description: Paclitaxel injection 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle；Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle； for 4 cycles
arm group label: GnRHa
arm group type: Experimental
description: Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Gonadotropin-releasing hormone agonist （GnRHa）11.25 mg every 3 months or 3.6mg every month subcutaneously
arm group label: letrozole
arm group type: Experimental
description: Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Letrozole 2.5mg/day
intervention type: Drug
intervention name: Paclitaxel
arm group label: Chemotherapy only
arm group label: GnRHa
arm group label: letrozole
other name: Taxol
intervention type: Drug
intervention name: Cisplatin
arm group label: Chemotherapy only
arm group label: GnRHa
arm group label: letrozole
intervention type: Drug
intervention name: Gonadotropin-releasing hormone agonist
description: Goserelin 3.6 mg q28d or Leuprolide 11.25 mg q3m
arm group label: GnRHa
intervention type: Drug
intervention name: Letrozole
arm group label: letrozole
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jinsong Lu
role: Principal Investigator
affiliation: RenJi Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: RenJi Hospital
investigator full name: Jinsong Lu
investigator title: professor
mesh term: Breast Neoplasms
mesh term: Inflammatory Breast Neoplasms
mesh term: Carcinoma, Ductal, Breast
mesh term: Paclitaxel
mesh term: Letrozole
mesh term: Hormones