xml: <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/NCT06009627</url>
    </required_header>
    <id_info>
      <org_study_id>Tianjin Hospital Cancer</org_study_id>
      <nct_id>NCT06009627</nct_id>
    </id_info>
    <brief_title>Study of Neoadjuvant Endocrine Therapy in HR Positive and HER2 Negative Premenopausal Breast Cancer Patients</brief_title>
    <official_title>Phase II Clinical Study of Darsilide Combined With Exemestane+Goserelin Neoadjuvant Endocrine Therapy in HR Positive and HER2 Negative Premenopausal Breast Cancer Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tianjin Medical University Cancer Institute and Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tianjin Medical University Cancer Institute and Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A multicenter, prospective, open, randomized cohort, non controlled phase II clinical study&#xD;
        to evaluate the effectiveness and safety of Darxil combined with Exemestane+goserelin&#xD;
        neoadjuvant endocrine therapy in HR positive and HER2 negative premenopausal breast cancer&#xD;
        patients. The study object was to evaluate the HR positive and HER2 negative premenopausal&#xD;
        breast cancer patients with SD after 2 cycles of neoadjuvant chemotherapy. The main endpoint&#xD;
        was the objective response rate (ORR) of treatment&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A multicenter, prospective, open, randomized cohort, non controlled phase II clinical study&#xD;
        to evaluate the effectiveness and safety of Darxil combined with Exemestane+goserelin&#xD;
        neoadjuvant endocrine therapy in HR positive and HER2 negative premenopausal breast cancer&#xD;
        patients. The study object was to evaluate the HR positive and HER2 negative premenopausal&#xD;
        breast cancer patients with SD after 2 cycles of neoadjuvant chemotherapy. The main endpoint&#xD;
        was the objective response rate (ORR) of treatment。Objective: To evaluate the efficacy and&#xD;
        safety of darsilide combined with endocrine therapy in SD patients with HR positive and HER2&#xD;
        negative premenopausal breast cancer after 2 cycles of neoadjuvant chemotherapy. It is&#xD;
        planned to recruit 119 HR positive and HER2 negative premenopausal breast cancer patients in&#xD;
        Group A to conduct the trial with Simon's two-stage design. The null hypothesis is a true&#xD;
        response rate of 0.2, while the alternative hypothesis is a true response rate of 0.4. The&#xD;
        experiment was conducted in two stages. In the first stage, 13 patients were enrolled. If&#xD;
        there are ≤ 3 responses in 13 patients, the study will be stopped Early stopping. Otherwise,&#xD;
        continue30 patients were enrolled, with a total sample size of 43. If there are ≥ 13 patients&#xD;
        responding, the treatment is effective. Group B was randomly assigned in a 1:1 ratio, with&#xD;
        the same number of participants as Group A, resulting in 43 final participants. Calculated&#xD;
        based on the proportion of SD patients in 2 cycles of neoadjuvant chemotherapy accounting for&#xD;
        80%, and considering a 10% dropout rate, the final enrollment was made The sample size is 119&#xD;
        cases. The actual samples for molecular testing can be randomly selected based on clinical&#xD;
        efficacy, with a statistically significant number.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 11, 2023</start_date>
    <completion_date type="Anticipated">September 11, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 11, 2025</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>Single (Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective response rate (ORR) for treatment</measure>
      <time_frame>At the end of the second cycle (each cycle is 21 or 28 days)</time_frame>
      <description>The proportion of patients whose tumor volume has shrunk to a predetermined value and can maintain the minimum time limit requirement</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Tumor residual load</measure>
      <time_frame>At the end of the 6 cycle (each cycle is 21 or 28 days)</time_frame>
      <description>The number of cancer cells, tumor size, or total number of cancer lesions in the human body after surgery</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Breast retention rate</measure>
      <time_frame>At the end of the 6 cycle (each cycle is 21 or 28 days)</time_frame>
      <description>Postoperative breast preservation ratio</description>
    </other_outcome>
    <other_outcome>
      <measure>Event free lifetime</measure>
      <time_frame>At the end of the 6 cycle (each cycle is 21 or 28 days)</time_frame>
      <description>The time from the start of randomized clinical trials to the progression of tumors (in any aspect) or death from any cause</description>
    </other_outcome>
    <other_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>2years</time_frame>
      <description>Time from randomization to death from any cause</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">119</enrollment>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Dalcelli+Goserelin+Exemestane</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>SD patients undergoing 2 cycles of preoperative treatment were randomly assigned to Group A and received darcelli, Exemestane, and Goserelin</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Docetaxel, epirubicin hydrochloride, Cyclophosphamide</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>SD patients undergoing 2 cycles of preoperative treatment were randomly assigned to Group B and received TAC chemotherapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dalcelli、Exemestane、Gosserine</intervention_name>
      <description>Dalcelli: once a day, 125 mg each time, taken for 3 weeks, stopped for 1 week, 1 for 4 weeks&#xD;
  Period. It is recommended to take the medication at approximately the same time every day, delivered in warm water, on an empty stomach, at least before taking the medication&#xD;
  Fasting for 1 hour before and after.&#xD;
  Exemestane: 25mg, oral, once a day, continuous administration.&#xD;
  Gosserine: 3.6mg, subcutaneous injection, once every four weeks, continuous administration</description>
      <arm_group_label>Dalcelli+Goserelin+Exemestane</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Docetaxel for injection、Epirubicin hydrochloride for injection、Cyclophosphamide for injection</intervention_name>
      <description>Docetaxel for injection: 75mg/m2, intravenous drip, approximately 30 minutes. Dose reduction and delayed administration are allowed every three weeks, with a maximum of three weeks of delayed administration allowed since the last administration time&#xD;
  Calculate, otherwise terminate treatment.&#xD;
  5. Epirubicin hydrochloride for injection: 75mg/m2, intravenous drip. Once every three weeks, allowing for dose reduction&#xD;
  And delayed administration, with a maximum allowable delay of 3 weeks, calculated from the last administration time. Otherwise&#xD;
  Stop treatment.&#xD;
  6. Cyclophosphamide for injection: 500mg/m2, intravenous drip. Once every three weeks, allowing for dose reduction and&#xD;
  Delayed administration, allowed up to 3 weeks, calculated from the last administration time, otherwise terminated treat</description>
      <arm_group_label>Docetaxel, epirubicin hydrochloride, Cyclophosphamide</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  All patients were operable estrogen receptor (ER) positive (&gt;1%), regardless of PR&#xD;
               expression level, HER2 receptor negative invasive breast cancer. Follow the 2018&#xD;
               ASCO-CAP HER2 negative interpretation guideline standard. Confirmed by the&#xD;
               pathological laboratory that the immunohistochemical (IHC) score is 0 or 1-2+and the&#xD;
               in situ hybridization (ISH) test is negative (ISH amplification rate&lt;2.0);&#xD;
  &#xD;
            -  Stage II-III initial treatment patients whose tumor staging meets the AJCC 8th edition&#xD;
               standards;&#xD;
  &#xD;
            -  At least one measurable breast and/or axillary disease;&#xD;
  &#xD;
            -  ECOG 0-1, with an estimated lifespan of at least 12 months;&#xD;
  &#xD;
            -  The functional level of the main organs must meet the following requirements:&#xD;
  &#xD;
          Blood routine: ANC ≥ 1.5 × ten9/L; PLT ≥ 90 × ten9/L; Hb ≥ 90 g/L;Blood biochemistry: TBIL&#xD;
          ≤ 2.5 × ULN; ALT and AST ≤ 2.5 × ULN; BUN and Cr≤ 1.5 × ULN;&#xD;
  &#xD;
            -  Lead ECG: QT interval (QTcF) corrected by Fridericia method&lt;470 ms for women;&#xD;
  &#xD;
            -  Able to accept all puncture biopsies required by the protocol;&#xD;
  &#xD;
            -  Volunteer to join this study, sign informed consent, have good compliance, and be&#xD;
               willing to cooperate with follow-up;&#xD;
  &#xD;
            -  Women with fertility potential must have a negative Pregnancy test (urine or serum)&#xD;
               within 7 days after administration,&#xD;
  &#xD;
          And agree to use acceptable birth control methods during the study period to avoid&#xD;
          pregnancy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Received any form of anti-tumor treatment within 28 days prior to the start of the&#xD;
               study;&#xD;
  &#xD;
            -  Simultaneously receiving any anti-tumor treatment beyond the provisions of other&#xD;
               protocols;&#xD;
  &#xD;
            -  Bilateral breast cancer, inflammatory breast cancer or occult breast;&#xD;
  &#xD;
            -  Stage IV breast cancer;&#xD;
  &#xD;
            -  Severe dysfunction of important organs such as heart, liver, and kidney;&#xD;
  &#xD;
            -  Unable to swallow, chronic diarrhea and Bowel obstruction, there are many factors that&#xD;
               affect drug taking and absorption;&#xD;
  &#xD;
            -  Participated in other drug clinical trials within 4 weeks prior to enrollment;&#xD;
  &#xD;
            -  Those with a known history of allergies to the drug components of this protocol; Have&#xD;
               a history of immunodeficiency, including positive Diagnosis of HIV/AIDS test Sex, HCV,&#xD;
               active hepatitis B, or other acquired or congenital immunodeficiency diseases Illness&#xD;
               or a history of organ transplantation;&#xD;
  &#xD;
            -  Have ever suffered from any heart disease, including: (1) arrhythmia that requires&#xD;
               medication or has clinical significance&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>100 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>jie 1 ge, 1</last_name>
      <role>Study Director</role>
      <affiliation>yes</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>xuejing 1 liu, 1</last_name>
      <phone>19502151516</phone>
      <email>lxj8109@126.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Jie Ge</name>
        <address>
          <city>Tianjin</city>
          <state>Tianjin</state>
          <zip>300000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>xuejing 1 liu, 1</last_name>
        <phone>19502151516</phone>
        <email>lxj8109@126.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 20, 2023</last_update_submitted>
    <last_update_submitted_qc>August 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</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>Cyclophosphamide</mesh_term>
      <mesh_term>Docetaxel</mesh_term>
      <mesh_term>Epirubicin</mesh_term>
      <mesh_term>Exemestane</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06009627
  org study id: Tianjin Hospital Cancer
  nct id: NCT06009627
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  A multicenter, prospective, open, randomized cohort, non controlled phase II clinical study
        to evaluate the effectiveness and safety of Darxil combined with Exemestane+goserelin
        neoadjuvant endocrine therapy in HR positive and HER2 negative premenopausal breast cancer
        patients. The study object was to evaluate the HR positive and HER2 negative premenopausal
        breast cancer patients with SD after 2 cycles of neoadjuvant chemotherapy. The main endpoint
        was the objective response rate (ORR) of treatment
  A multicenter, prospective, open, randomized cohort, non controlled phase II clinical study
        to evaluate the effectiveness and safety of Darxil combined with Exemestane+goserelin
        neoadjuvant endocrine therapy in HR positive and HER2 negative premenopausal breast cancer
        patients. The study object was to evaluate the HR positive and HER2 negative premenopausal
        breast cancer patients with SD after 2 cycles of neoadjuvant chemotherapy. The main endpoint
        was the objective response rate (ORR) of treatment。Objective: To evaluate the efficacy and
        safety of darsilide combined with endocrine therapy in SD patients with HR positive and HER2
        negative premenopausal breast cancer after 2 cycles of neoadjuvant chemotherapy. It is
        planned to recruit 119 HR positive and HER2 negative premenopausal breast cancer patients in
        Group A to conduct the trial with Simon's two-stage design. The null hypothesis is a true
        response rate of 0.2, while the alternative hypothesis is a true response rate of 0.4. The
        experiment was conducted in two stages. In the first stage, 13 patients were enrolled. If
        there are ≤ 3 responses in 13 patients, the study will be stopped Early stopping. Otherwise,
        continue30 patients were enrolled, with a total sample size of 43. If there are ≥ 13 patients
        responding, the treatment is effective. Group B was randomly assigned in a 1:1 ratio, with
        the same number of participants as Group A, resulting in 43 final participants. Calculated
        based on the proportion of SD patients in 2 cycles of neoadjuvant chemotherapy accounting for
        80%, and considering a 10% dropout rate, the final enrollment was made The sample size is 119
        cases. The actual samples for molecular testing can be randomly selected based on clinical
        efficacy, with a statistically significant number.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Investigator)
  measure: Objective response rate (ORR) for treatment
  time frame: At the end of the second cycle (each cycle is 21 or 28 days)
  description: The proportion of patients whose tumor volume has shrunk to a predetermined value and can maintain the minimum time limit requirement
  measure: Tumor residual load
  time frame: At the end of the 6 cycle (each cycle is 21 or 28 days)
  description: The number of cancer cells, tumor size, or total number of cancer lesions in the human body after surgery
  measure: Breast retention rate
  time frame: At the end of the 6 cycle (each cycle is 21 or 28 days)
  description: Postoperative breast preservation ratio
  measure: Event free lifetime
  time frame: At the end of the 6 cycle (each cycle is 21 or 28 days)
  description: The time from the start of randomized clinical trials to the progression of tumors (in any aspect) or death from any cause
  measure: Overall survival (OS)
  time frame: 2years
  description: Time from randomization to death from any cause
  arm group label: Dalcelli+Goserelin+Exemestane
  arm group type: Experimental
  description: SD patients undergoing 2 cycles of preoperative treatment were randomly assigned to Group A and received darcelli, Exemestane, and Goserelin
  arm group label: Docetaxel, epirubicin hydrochloride, Cyclophosphamide
  arm group type: Active Comparator
  description: SD patients undergoing 2 cycles of preoperative treatment were randomly assigned to Group B and received TAC chemotherapy
  intervention type: Drug
  intervention name: Dalcelli、Exemestane、Gosserine
  description: Dalcelli: once a day, 125 mg each time, taken for 3 weeks, stopped for 1 week, 1 for 4 weeks
  Period. It is recommended to take the medication at approximately the same time every day, delivered in warm water, on an empty stomach, at least before taking the medication
  Fasting for 1 hour before and after.
  Exemestane: 25mg, oral, once a day, continuous administration.
  Gosserine: 3.6mg, subcutaneous injection, once every four weeks, continuous administration
  arm group label: Dalcelli+Goserelin+Exemestane
  intervention type: Drug
  intervention name: Docetaxel for injection、Epirubicin hydrochloride for injection、Cyclophosphamide for injection
  description: Docetaxel for injection: 75mg/m2, intravenous drip, approximately 30 minutes. Dose reduction and delayed administration are allowed every three weeks, with a maximum of three weeks of delayed administration allowed since the last administration time
  Calculate, otherwise terminate treatment.
  5. Epirubicin hydrochloride for injection: 75mg/m2, intravenous drip. Once every three weeks, allowing for dose reduction
  And delayed administration, with a maximum allowable delay of 3 weeks, calculated from the last administration time. Otherwise
  Stop treatment.
  6. Cyclophosphamide for injection: 500mg/m2, intravenous drip. Once every three weeks, allowing for dose reduction and
  Delayed administration, allowed up to 3 weeks, calculated from the last administration time, otherwise terminated treat
  arm group label: Docetaxel, epirubicin hydrochloride, Cyclophosphamide
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: 100 Years
  healthy volunteers: No
  last name: jie 1 ge, 1
  role: Study Director
  affiliation: yes
  last name: xuejing 1 liu, 1
  phone: 19502151516
  email: lxj8109@126.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Cyclophosphamide
  mesh term: Docetaxel
  mesh term: Epirubicin
  mesh term: Exemestane
  sharing ipd: No