<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/NCT02973737</url>
  </required_header>
  <id_info>
    <org_study_id>HR-BLTN-Ⅲ-MBC-A</org_study_id>
    <nct_id>NCT02973737</nct_id>
  </id_info>
  <brief_title>A Study of Pyrotinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer</brief_title>
  <official_title>Pyrotinib Plus Capecitabine Versus Placebo Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer:a Randomised, Double-blind, Multicentre, Phase 3 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This&#xD;
      study is a randomized, multi-center, multinational, double blind, active-controlled, parallel&#xD;
      design study of the combination of pyrotinib in combination with capecitabine versus placebo&#xD;
      plus capecitabine in HER2+ MBC patients, who have prior received anthracyclin, taxane and&#xD;
      trastuzumab.&#xD;
&#xD;
      Patients will be randomized in a 2:1 ratio to one of the following treatment arms:&#xD;
&#xD;
      Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo&#xD;
      (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm&#xD;
      of therapy until the occurrence of death, disease progression, unacceptable toxicity, or&#xD;
      other specified withdrawal criterion.&#xD;
&#xD;
      Patients in control group can be provide pyrotinib treatment when they progressed after the&#xD;
      placebo plus capecitabine treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a phase 3, randomized, multi-center, multinational, double blind,&#xD;
      active-controlled, parallel design study of the combination of pyrotinib in combination with&#xD;
      capecitabine versus placebo plus capecitabine in HER2+ MBC patients, who have prior received&#xD;
      anthracyclin, taxane and trastuzumab.&#xD;
&#xD;
      Patients will be randomized in a 2:1 ratio to one of the following treatment arms:&#xD;
&#xD;
      Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo&#xD;
      (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm&#xD;
      of therapy until the occurrence of death, disease progression, unacceptable toxicity, or&#xD;
      other specified withdrawal criterion.&#xD;
&#xD;
      Efficacy assessments will be performed at screening, every 6 weeks until cycle 18, every 12&#xD;
      weeks thereafter.&#xD;
&#xD;
      Patients in control group can be provide pyrotinib treatment when they progressed after the&#xD;
      placebo plus capecitabine treatment. Pyrotinb will be administrated until the patients&#xD;
      reached progress again or wit&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 20, 2016</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Estimated 10 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Estimated 10 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety(adverse Events [AEs] and Serious Adverse Events [SAEs])</measure>
    <time_frame>From infromed consent through 28 days following treatment completion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Estimated 10 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit rate (CBR)</measure>
    <time_frame>Estimated 10 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Estimated 30 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">279</enrollment>
  <condition>HER2 Positive Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pyrotinib plus capecitabine pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>arm 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>placebo plus capecitabine placebo(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pyrotinib</intervention_name>
    <description>400 mg once daily</description>
    <arm_group_label>arm 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>400 mg once daily</description>
    <arm_group_label>arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>1000 mg/m2 per day on day 1 through 14, every 21 days.</description>
    <arm_group_label>arm 1</arm_group_label>
    <arm_group_label>arm 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged ≥18 and ≤75 years.&#xD;
&#xD;
          2. ECOG performance status of 0 to 1.&#xD;
&#xD;
          3. Life expectancy of more than 12 weeks.&#xD;
&#xD;
          4. According to RECIST 1.1, at least one measurable lesion exists&#xD;
&#xD;
          5. Histologically or cytologic confirmed HER2 positive advanced breast cancer which&#xD;
             failed prior therapies.&#xD;
&#xD;
          6. Prior treatment with trastuzumab(≥2 cycles in the metastatic setting, or ≥3 months in&#xD;
             adjuvant setting), and the patients are not available for the trastuzumab or lapatinib&#xD;
&#xD;
          7. Previously reveived both Anthracyclin and Taxane.&#xD;
&#xD;
          8. Required laboratory values including following parameters:&#xD;
&#xD;
             ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 90 x 10^9/L; Hemoglobin: ≥ 9.0 g/dL; Total&#xD;
             bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2 x ULN(patients with&#xD;
             liver metastases: &lt;/= 5 x ULN); BUN and Creatinine: ≤ 1.5 x ULN;LVEF: ≥ 50%;QTcF: &lt;&#xD;
             470 ms.&#xD;
&#xD;
          9. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received previous therapy with lapatinib, neratinib, pyrotinib or any other HER2&#xD;
             directe tyrosine kinase inhibitor.&#xD;
&#xD;
          2. Received previous therapy with capecitabine.&#xD;
&#xD;
          3. History of receiving chemotherapy, target-therapy or investigational treatment within&#xD;
             28 days prior to randomization. Received hormone therapy within 7 days prior to&#xD;
             randomization.&#xD;
&#xD;
          4. Brain metastases that are untreated, symptomatic, or require therapy to control&#xD;
             symptoms.&#xD;
&#xD;
          5. Current severe, uncontrolled systemic disease.&#xD;
&#xD;
          6. Unable or unwilling to swallow tablets.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>307 Hospital Affiliated to Academy Military Medical Science</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</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>Capecitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02973737
org study id: HR-BLTN-Ⅲ-MBC-A
nct id: NCT02973737
lead sponsor: 
has dmc: No
Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This
      study is a randomized, multi-center, multinational, double blind, active-controlled, parallel
      design study of the combination of pyrotinib in combination with capecitabine versus placebo
      plus capecitabine in HER2+ MBC patients, who have prior received anthracyclin, taxane and
      trastuzumab.

      Patients will be randomized in a 2:1 ratio to one of the following treatment arms:

      Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo
      (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm
      of therapy until the occurrence of death, disease progression, unacceptable toxicity, or
      other specified withdrawal criterion.

      Patients in control group can be provide pyrotinib treatment when they progressed after the
      placebo plus capecitabine treatment.
This study is a phase 3, randomized, multi-center, multinational, double blind,
      active-controlled, parallel design study of the combination of pyrotinib in combination with
      capecitabine versus placebo plus capecitabine in HER2+ MBC patients, who have prior received
      anthracyclin, taxane and trastuzumab.

      Patients will be randomized in a 2:1 ratio to one of the following treatment arms:

      Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo
      (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm
      of therapy until the occurrence of death, disease progression, unacceptable toxicity, or
      other specified withdrawal criterion.

      Efficacy assessments will be performed at screening, every 6 weeks until cycle 18, every 12
      weeks thereafter.

      Patients in control group can be provide pyrotinib treatment when they progressed after the
      placebo plus capecitabine treatment. Pyrotinb will be administrated until the patients
      reached progress again or wit
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Progression Free Survival (PFS)
time frame: Estimated 10 months
measure: Objective Response Rate (ORR)
time frame: Estimated 10 months
measure: Safety(adverse Events [AEs] and Serious Adverse Events [SAEs])
time frame: From infromed consent through 28 days following treatment completion
measure: Duration of Response (DOR)
time frame: Estimated 10 months
measure: Clinical Benefit rate (CBR)
time frame: Estimated 10 months
measure: Overall Survival (OS)
time frame: Estimated 30 months
arm group label: arm 1
arm group type: Experimental
description: pyrotinib plus capecitabine pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)
arm group label: arm 2
arm group type: Active Comparator
description: placebo plus capecitabine placebo(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)
intervention type: Drug
intervention name: pyrotinib
description: 400 mg once daily
arm group label: arm 1
intervention type: Drug
intervention name: placebo
description: 400 mg once daily
arm group label: arm 2
intervention type: Drug
intervention name: Capecitabine
description: 1000 mg/m2 per day on day 1 through 14, every 21 days.
arm group label: arm 1
arm group label: arm 2
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Capecitabine
sharing ipd: Yes