<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/NCT04407988</url>
  </required_header>
  <id_info>
    <org_study_id>HR-BLTN-008</org_study_id>
    <nct_id>NCT04407988</nct_id>
  </id_info>
  <brief_title>Pyrotinib in Combination With Letrozole in Patients With HER2-Positive, ER-Positive Metastatic Breast Cancer</brief_title>
  <official_title>Phase II Study of Pyrotinib in Combination With Letrozole in Patients With HER2-Positive, ER-Positive Metastatic Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hunan Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hunan Cancer Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, single-arm, multi-center clinical study of pyrotinib in combination&#xD;
      With letrozole in patients With HER2-Positive, ER-Positive metastatic breast cancer. Our aim&#xD;
      was to explore the efficacy and safety of pyrotinib combined with letrozole in patients with&#xD;
      HER2-positive, ER-positive metastatic breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ER+/HER2+ metastatic breast cancer is a special subtype of HER2+ breast cancer. General&#xD;
      guidelines recommend chemotherapy combined with HER2-targeted therapy for this subtype of&#xD;
      patients. However, for the highly selected patients with ER- positive/HER2-positive ABC, ET +&#xD;
      anti-HER2 therapy could be chosen as first-line therapy. And Pyrotinib is an oral tyrosine&#xD;
      kinase inhibitor targeting both HER-1 and HER-2 receptors. Therefore this study is planned to&#xD;
      enroll 86 patients with HER2-positive, ER-positive metastatic breast cancer receiving&#xD;
      first-line treatment with pyrotinib and letrozole. The main purpose was to evaluate the&#xD;
      efficacy and safety of pyrotinib combined with letrozole in patients with HER2-positive,&#xD;
      ER-positive metastatic breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 6, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>
    <intervention_model_description>Pyrotinib plus Letrozole</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Benefit rate (CBR)</measure>
    <time_frame>Estimated 12 months</time_frame>
    <description>Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Estimated 12 months</time_frame>
    <description>Ratio of CR and PR in all subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Estimated 12 months</time_frame>
    <description>From enrollment to progression or death (for any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Estimated 24 months</time_frame>
    <description>From enrollment to death (for any reason)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events and Serious Adverse Events</measure>
    <time_frame>From informed consent through 28 days following treatment completion</time_frame>
    <description>Adverse events are described in terms of CTC AE 4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">86</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Pyrotinib plus Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pyrotinib Maleate plus Letrozole</intervention_name>
    <description>pyrotinib(400 mg once daily) + Letrozole (2.5 mg once daily)</description>
    <arm_group_label>Pyrotinib plus Letrozole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with HER2+/ER+ recurrent or metastatic breast cancer confirmed by&#xD;
             histopathology;&#xD;
&#xD;
               -  HER2 positive: HER2 IHC 3+, or HER2 IHC 2+ and ISH positive&#xD;
&#xD;
               -  ER positive: the percentage of cells positive for ER expression ≥ 10%&#xD;
&#xD;
          2. Premenopausal, perimenopausal or postmenopausal patients (with OFS, if pre- or&#xD;
             perimenopausal);&#xD;
&#xD;
          3. If the patient is bilateral breast cancer, metastasis lesions must be HER2 and ER&#xD;
             positive;&#xD;
&#xD;
          4. 18-70 years old;&#xD;
&#xD;
          5. ECOG PS 0～1;&#xD;
&#xD;
          6. Life expectancy is not less than 12 weeks;&#xD;
&#xD;
          7. At least one measurable lesion according to RECIST 1.1;&#xD;
&#xD;
          8. Prior (neo) adjuvant trastuzumab, pertuzumab or chemotherapy were eligible, and the&#xD;
             disease free interval must be greater than 12 months from completion of (neo) adjuvant&#xD;
             trastuzumab and pertuzumab to metastatic diagnosis;&#xD;
&#xD;
          9. Prior (neo) adjuvant hormone therapy was allowed, if received adjuvant AI, the disease&#xD;
             free interval must be greater than 12 months from the completion of treatment;&#xD;
&#xD;
         10. Disease-free Survival after surgery (DFS) ≥12 months;&#xD;
&#xD;
         11. Patients with adequate organ function before enrollment: ANC ≥ 1.5×109/L, PLT ≥&#xD;
             75×109/L, Hb ≥ 100 g/L; TBIL≤1.0ULN；ALT and AST≤3×ULN (ALT and AST≤5×ULN if liver&#xD;
             metastasis); BUN and Cr≤1.5×ULN and CCr≥50 mL/min; LVEF ≥ 50% and QTc &lt; 480 ms;&#xD;
&#xD;
         12. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Central nervous system metastasis;&#xD;
&#xD;
          2. patients with Visceral crisis;&#xD;
&#xD;
          3. Unable to swallow, chronic diarrhea and intestinal obstruction, there are many factors&#xD;
             affecting drug use and absorption;&#xD;
&#xD;
          4. received radiotherapy, hormone therapy, chemotherapy, surgery (excluding local&#xD;
             puncture) or molecular targeted therapy for advanced or metastatic disease;&#xD;
&#xD;
          5. received radiotherapy, chemotherapy, surgery (excluding local puncture) or molecular&#xD;
             targeted therapy within 4 weeks prior to randomization;&#xD;
&#xD;
          6. Received hormone therapy within 2 weeks prior to randomization;&#xD;
&#xD;
          7. Participated in other clinical trial within 4 weeks prior to randomization;&#xD;
&#xD;
          8. Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors (lapatinib,&#xD;
             neratinib or pyrotinib);&#xD;
&#xD;
          9. Other malignancies within 5 years, except for cured skin basal cell&#xD;
             carcinoma,carcinoma in-situ of uterine cervix and squamous-cell carcinoma;&#xD;
&#xD;
         10. Receive other anti-tumour therapy at the same time;&#xD;
&#xD;
         11. History of immunodeficiency, including HIV positive, HCV, active hepatitis B, or other&#xD;
             acquired, congenital immunodeficiency disorders, or organ transplantation, is known;&#xD;
&#xD;
         12. History of any kind of Heart disease;&#xD;
&#xD;
         13. All female patients in pregnancy or breastfeeding period, fertile women with positive&#xD;
             baseline pregnancy tests;&#xD;
&#xD;
         14. Evidence of significant medical illness that will substantially increase the risk on&#xD;
             the participation or completion of the study in the investigator's judgment. Examples&#xD;
             included, but not limited to, hypertension, severe diabetes, etc;&#xD;
&#xD;
         15. History of neurological or psychiatric disorders, including epilepsy or dementia;&#xD;
&#xD;
         16. Patients not eligible for this study judged by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Quchang Ouyang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Breast Cancer Medical Oncology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Quchang Ouyang, PhD</last_name>
    <phone>+86 13973135318</phone>
    <email>Oyqc1969@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hunan Cancer Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410006</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Quchang Ouyang, PhD</last_name>
      <phone>+86 13973135318</phone>
      <email>Oyqc1969@126.com</email>
    </contact>
    <investigator>
      <last_name>Quchang Ouyang, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>October 12, 2021</last_update_submitted>
  <last_update_submitted_qc>October 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2021</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>Letrozole</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/NCT04407988
org study id: HR-BLTN-008
nct id: NCT04407988
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a prospective, single-arm, multi-center clinical study of pyrotinib in combination
      With letrozole in patients With HER2-Positive, ER-Positive metastatic breast cancer. Our aim
      was to explore the efficacy and safety of pyrotinib combined with letrozole in patients with
      HER2-positive, ER-positive metastatic breast cancer.
ER+/HER2+ metastatic breast cancer is a special subtype of HER2+ breast cancer. General
      guidelines recommend chemotherapy combined with HER2-targeted therapy for this subtype of
      patients. However, for the highly selected patients with ER- positive/HER2-positive ABC, ET +
      anti-HER2 therapy could be chosen as first-line therapy. And Pyrotinib is an oral tyrosine
      kinase inhibitor targeting both HER-1 and HER-2 receptors. Therefore this study is planned to
      enroll 86 patients with HER2-positive, ER-positive metastatic breast cancer receiving
      first-line treatment with pyrotinib and letrozole. The main purpose was to evaluate the
      efficacy and safety of pyrotinib combined with letrozole in patients with HER2-positive,
      ER-positive metastatic breast cancer.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Pyrotinib plus Letrozole
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical Benefit rate (CBR)
time frame: Estimated 12 months
description: Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects
measure: Objective Response Rate (ORR)
time frame: Estimated 12 months
description: Ratio of CR and PR in all subjects
measure: Progression Free Survival (PFS)
time frame: Estimated 12 months
description: From enrollment to progression or death (for any reason
measure: Overall Survival (OS)
time frame: Estimated 24 months
description: From enrollment to death (for any reason)
measure: Adverse Events and Serious Adverse Events
time frame: From informed consent through 28 days following treatment completion
description: Adverse events are described in terms of CTC AE 4.0
arm group label: Pyrotinib plus Letrozole
arm group type: Experimental
intervention type: Drug
intervention name: Pyrotinib Maleate plus Letrozole
description: pyrotinib(400 mg once daily) + Letrozole (2.5 mg once daily)
arm group label: Pyrotinib plus Letrozole
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Quchang Ouyang, PhD
role: Principal Investigator
affiliation: Department of Breast Cancer Medical Oncology
last name: Quchang Ouyang, PhD
phone: +86 13973135318
email: Oyqc1969@126.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Letrozole