<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/NCT03264547</url>
  </required_header>
  <id_info>
    <org_study_id>JBCRG-M06</org_study_id>
    <nct_id>NCT03264547</nct_id>
  </id_info>
  <brief_title>A Study to Compare Eribulin Mesylate + Pertuzumab + Trastuzumab With Paclitaxel or Docetaxel + Pertuzumab + Trastuzumab</brief_title>
  <official_title>A Phase III Clinical Study to Compare the Combination Therapy of Eribulin Mesylate + Pertuzumab + Trastuzumab With Paclitaxel or Docetaxel + Pertuzumab + Trastuzumab (EMERALD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Japan Breast Cancer Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eisai Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Japan Breast Cancer Research Group</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To verify that combination therapy with trastuzumab + pertuzumab + eribulin brings similar&#xD;
      PFS and better QOL compared to trastuzumab + pertuzumab + taxane in advanced/recurrent&#xD;
      HER2-positive breast cancer patients who have no medical history of chemotherapy except&#xD;
      ado-trastuzumab emtansine&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Anticipated">October 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2022</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>PFS</measure>
    <time_frame>5.75 years</time_frame>
    <description>Progression-free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RR</measure>
    <time_frame>5.75 years</time_frame>
    <description>Response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DR</measure>
    <time_frame>5.75 years</time_frame>
    <description>Duration of response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>6.25 years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PRO</measure>
    <time_frame>5.75 years</time_frame>
    <description>Patient-reported outcomes(Numbness &amp; tingling)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>5.75 years</time_frame>
    <description>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomaker</measure>
    <time_frame>5.75 years</time_frame>
    <description>DNA mutation in the ctDNA and tumor tissue such as HER2,HER3, and PIK3CA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nMFS</measure>
    <time_frame>5.75 years</time_frame>
    <description>new Metastases free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTF of the subsequent treatment</measure>
    <time_frame>5.75 years</time_frame>
    <description>Treatment duration of the following treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">480</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Trastuzumab + pertuzumab + Taxane*&#xD;
*Taxane is chosen from the following; Docetaxel or Paclitaxel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trastuzumab+ Pertuzumab + Eribulin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pertuzumab</intervention_name>
    <description>Every 3 weeks</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Perjeta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Every 3 weeks</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Every 3 weeks</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Every week</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>Taxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eribulin</intervention_name>
    <description>Administered for 2 weeks and is then stopped to be administered for 1 week</description>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Halaven</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with breast cancer that is confirmed histologically or cytologically&#xD;
&#xD;
          2. Patients who are confirmed to be HER2 positive for the primary or a metastatic lesion&#xD;
             at a participating medical institution&#xD;
&#xD;
          3. Patients with no medical history of treatment for advanced/recurrent cancer using a&#xD;
             regimen of drugs including chemotherapeutics&#xD;
&#xD;
          4. &gt;=6 months have passed since perioperative treatment with anticancer agents&#xD;
&#xD;
          5. Presence of a measurable lesion not required&#xD;
&#xD;
          6. Female aged 20-70 years old at the time of consent acquisition&#xD;
&#xD;
          7. Baseline left ventricular ejection fraction (LVEF) measured by ECHO or MUGA of &gt;=50%&#xD;
&#xD;
          8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1&#xD;
&#xD;
          9. Patients who have maintained major organ functions, meeting all of the following&#xD;
             criteria on a test within 28 days before enrollment. If there are multiple test&#xD;
             results during this period, that obtained immediately before enrollment should be&#xD;
             adopted.&#xD;
&#xD;
        (1) Neutrophil count: &gt;=1,500/mm3 (2) Platelet count: &gt;=100,000/mm 3 (3) Hemoglobin: &gt;=9.0&#xD;
        g/dL (4) Total bilirubin: &lt;=1.5 mg/dL (5) AST (GOT), ALT (GPT): &lt;=2.5 times the ULN (&lt;=5&#xD;
        times in those with liver metastasis) (6) Serum creatinine: &lt;=1.5 mg/dL 10) Patients with a&#xD;
        life expectancy of at least 6 months 11) Patient who submits written consent herself after&#xD;
        receiving sufficient explanation about this study 12) Patients who can undergo QOL&#xD;
        investigation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients planning to undergo radical surgery if they respond to a treatment&#xD;
&#xD;
          2. Patients who have non-hematological adverse events assessed as Grade &gt;=3 in the Common&#xD;
             Terminology Criteria for Adverse Events ver. 4.0 in the Japanese JCOG version (CTCAE&#xD;
             v4.0-JCOG) at the time of enrollment&#xD;
&#xD;
          3. Patients who have symptomatic metastases to the central nervous system or whose&#xD;
             symptoms are hard to control&#xD;
&#xD;
          4. Patients who have active double cancer&#xD;
&#xD;
          5. Patients who have poorly controlled hypertension, or unstable angina&#xD;
&#xD;
          6. Patients who have a past history of congestive heart failure assessed as Class ll or&#xD;
             higher in the New York Heart Association (NYHA) classification, or clinically&#xD;
             significant arrhythmia requiring treatment&#xD;
&#xD;
          7. Patients with a past history of myocardial infarction within 6 months before&#xD;
             enrollment&#xD;
&#xD;
          8. Patients who are expected to undergo major surgical treatment or who had severe injury&#xD;
             within 28 days before enrollment, or who require major surgical treatment during the&#xD;
             study treatment period&#xD;
&#xD;
          9. Patients with interstitial pneumonia which is symptomatic or requires treatment&#xD;
&#xD;
         10. Pregnant women, those with a positive pregnancy test, and lactating women&#xD;
&#xD;
         11. Patients with active systemic infection (including HCV and HBV), or who are found to&#xD;
             be HIV-positive&#xD;
&#xD;
         12. Patients with hypersensitivity against pertuzumab and trastuzumab&#xD;
&#xD;
         13. Patients whom the investigator consider unable or unwilling to follow the protocol&#xD;
             requirements&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Toshinari Tamashita, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kanagawa Cancer Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Norikazu Masuda, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NHO Osaka National Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shigehira Saji, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fukushima Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Toshinari Tamashita, MD, PhD</last_name>
    <phone>+81-45-520-2222</phone>
    <email>tyamashita@kcch.jp</email>
  </overall_contact>
  <location>
    <facility>
      <name>Kanagawa Cancer Center</name>
      <address>
        <city>Yokohama</city>
        <state>Kanagawa</state>
        <zip>241-8515</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Toshinari Yamashita, MD,PhD</last_name>
      <phone>+81-45-520-2222</phone>
      <email>tyamashita@kcch.jp</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Osaka National Hospital</name>
      <address>
        <city>Ōsaka</city>
        <state>Osaka</state>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Norikazu Masuda, MD,PhD</last_name>
      <phone>+81-6-6942-1331</phone>
      <email>nmasuda@alpha.ocn.ne.jp</email>
    </contact>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <results_reference>
    <citation>Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.</citation>
    <PMID>22149875</PMID>
  </results_reference>
  <results_reference>
    <citation>Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Dieras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. doi: 10.1016/S0140-6736(11)60070-6. Epub 2011 Mar 2.</citation>
    <PMID>21376385</PMID>
  </results_reference>
  <results_reference>
    <citation>Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. doi: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.</citation>
    <PMID>25605862</PMID>
  </results_reference>
  <results_reference>
    <citation>Wilks S, Puhalla S, O'Shaughnessy J, Schwartzberg L, Berrak E, Song J, Cox D, Vahdat L. Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. Clin Breast Cancer. 2014 Dec;14(6):405-12. doi: 10.1016/j.clbc.2014.04.004. Epub 2014 Jun 2.</citation>
    <PMID>25024001</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>September 19, 2017</last_update_submitted>
  <last_update_submitted_qc>September 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Pertuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03264547
org study id: JBCRG-M06
nct id: NCT03264547
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To verify that combination therapy with trastuzumab + pertuzumab + eribulin brings similar
      PFS and better QOL compared to trastuzumab + pertuzumab + taxane in advanced/recurrent
      HER2-positive breast cancer patients who have no medical history of chemotherapy except
      ado-trastuzumab emtansine
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: 5.75 years
description: Progression-free survival
measure: RR
time frame: 5.75 years
description: Response rate
measure: DR
time frame: 5.75 years
description: Duration of response
measure: OS
time frame: 6.25 years
description: Overall survival
measure: PRO
time frame: 5.75 years
description: Patient-reported outcomes(Numbness & tingling)
measure: Safety
time frame: 5.75 years
description: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
measure: Biomaker
time frame: 5.75 years
description: DNA mutation in the ctDNA and tumor tissue such as HER2,HER3, and PIK3CA
measure: nMFS
time frame: 5.75 years
description: new Metastases free survival
measure: TTF of the subsequent treatment
time frame: 5.75 years
description: Treatment duration of the following treatment
arm group label: Arm A
arm group type: Active Comparator
description: Trastuzumab + pertuzumab + Taxane*
*Taxane is chosen from the following; Docetaxel or Paclitaxel
arm group label: Arm B
arm group type: Experimental
description: Trastuzumab+ Pertuzumab + Eribulin
intervention type: Drug
intervention name: Pertuzumab
description: Every 3 weeks
arm group label: Arm A
arm group label: Arm B
other name: Perjeta
intervention type: Drug
intervention name: Trastuzumab
description: Every 3 weeks
arm group label: Arm A
arm group label: Arm B
other name: Herceptin
intervention type: Drug
intervention name: Docetaxel
description: Every 3 weeks
arm group label: Arm A
other name: Taxotere
intervention type: Drug
intervention name: Paclitaxel
description: Every week
arm group label: Arm A
other name: Taxol
intervention type: Drug
intervention name: Eribulin
description: Administered for 2 weeks and is then stopped to be administered for 1 week
arm group label: Arm B
other name: Halaven
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: No
last name: Toshinari Tamashita, MD, PhD
role: Principal Investigator
affiliation: Kanagawa Cancer Center
last name: Norikazu Masuda, MD, PhD
role: Principal Investigator
affiliation: NHO Osaka National Hospital
last name: Shigehira Saji, MD, PhD
role: Principal Investigator
affiliation: Fukushima Medical University
last name: Toshinari Tamashita, MD, PhD
phone: +81-45-520-2222
email: tyamashita@kcch.jp
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Japan
citation: Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.
PMID: 22149875
citation: Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Dieras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. doi: 10.1016/S0140-6736(11)60070-6. Epub 2011 Mar 2.
PMID: 21376385
citation: Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. doi: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.
PMID: 25605862
citation: Wilks S, Puhalla S, O'Shaughnessy J, Schwartzberg L, Berrak E, Song J, Cox D, Vahdat L. Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. Clin Breast Cancer. 2014 Dec;14(6):405-12. doi: 10.1016/j.clbc.2014.04.004. Epub 2014 Jun 2.
PMID: 25024001
responsible party type: Sponsor
mesh term: Paclitaxel
mesh term: Docetaxel
mesh term: Trastuzumab
mesh term: Pertuzumab
sharing ipd: No