<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/NCT02214004</url>
  </required_header>
  <id_info>
    <org_study_id>HERAKLES</org_study_id>
    <nct_id>NCT02214004</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women</brief_title>
  <acronym>HERAKLES</acronym>
  <official_title>A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gangnam Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gangnam Severance Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate whether trastuzumab and letrozole are effective and&#xD;
      safe in the preoperative treatment for postmenopausal patients with hormone receptor-positive&#xD;
      and HER2-positive breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligibility criteria&#xD;
&#xD;
        -  Ages Eligible for Study: ≥ 20 years&#xD;
&#xD;
        -  Invasive cancer (clinical stage IB-IIIB)&#xD;
&#xD;
        -  Measurable tumor larger than 1cm&#xD;
&#xD;
        -  ECOG status 0 or 1&#xD;
&#xD;
        -  Postmenopausal women&#xD;
&#xD;
             -  Age ≥55 years and amenorrhea&#xD;
&#xD;
             -  Age &lt;55 years and amenorrhea for ≥12 months with FSH &gt;30 mIU/ml&#xD;
&#xD;
        -  HER2 positive tumor&#xD;
&#xD;
             -  3 positive on IHC&#xD;
&#xD;
             -  2 positive on IHC with HER2 gene amplification on FISH or SISH using a single-probe&#xD;
                or dual-probe&#xD;
&#xD;
        -  Estrogen receptor positive tumor&#xD;
&#xD;
             -  Positive ER expression with Allred score more than PS3/TS8 or modified Allred score&#xD;
                more than PS4/TS7&#xD;
&#xD;
        -  Eligible cardiac function&#xD;
&#xD;
             -  Normal heard evaluated by ECG&#xD;
&#xD;
                  -  Consider clinically non-significant arrythmia and ischemic change as normal&#xD;
&#xD;
             -  LVEF ≥ 55% measured by ECHO or MUGA scan&#xD;
&#xD;
      Outcome measures&#xD;
&#xD;
        -  Primary End-point&#xD;
&#xD;
             -  The rate of pathologic complete response (pCR)&#xD;
&#xD;
                  -  No residual invasive cancer in breast&#xD;
&#xD;
        -  Secondary End-point&#xD;
&#xD;
             -  Clinical Response Rate&#xD;
&#xD;
             -  Safety profiles for the preoperative use of concurrent trastuzumab and letrozole&#xD;
&#xD;
             -  The rate of breast conservative surgery&#xD;
&#xD;
             -  Total pathologic complete response (tpCR)&#xD;
&#xD;
                  -  No residual invasive cancer in breast and ipsilateral axilla&#xD;
&#xD;
             -  Analysis of biomarkers based on baseline specimen and residual tumor&#xD;
&#xD;
        -  Ki67 expression&#xD;
&#xD;
        -  cDNA microarray: gene expression profiling&#xD;
&#xD;
        -  Association between clinical response rate and circulating tumor cells (CTCs)&#xD;
&#xD;
             -  CTCs are measured by CytoGen (SEOUL, KOREA)&quot;&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>March 2015</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">March 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The rate of pathologic complete response</measure>
    <time_frame>At time of surgery</time_frame>
    <description>No residual invasive cancer in breast regardless of axilla</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Response Rate</measure>
    <time_frame>At time of surgery</time_frame>
    <description>Clinical response includes complete response, partial response and stable disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety profiles for the preoperative use of concurrent trastuzumab and letrozole</measure>
    <time_frame>Up to 3 months after surgery</time_frame>
    <description>Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The rate of breast conservative surgery</measure>
    <time_frame>Up to 3 weeks after surgery</time_frame>
    <description>The rate of breast conservative surgery among the patients receiving surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total pathologic complete response (tpCR)</measure>
    <time_frame>At time of surgery</time_frame>
    <description>No residual invasive cancer in breast and ipsilateral axilla</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of biomarkers based on baseline specimen and residual tumor</measure>
    <time_frame>Baseline and at time of surgery</time_frame>
    <description>Ki67 expression&#xD;
cDNA microarray: gene expression profiling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between clinical response rate and circulating tumor cells (CTCs)</measure>
    <time_frame>Baseline and at time of surgery</time_frame>
    <description>Association between clinical response rate and circulating tumor cells (CTCs)&#xD;
: CTCs are measured by CytoGen (SEOUL, KOREA)&quot;</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">132</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Trastuzumab and Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>- Concurrently initiate two drugs on Day 1 of Cycle 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>- Eight times IV administration of trastuzumab per 3 weeks&#xD;
Trastuzumab 8mg/kg on Day 1 of Cycle 1&#xD;
Trastuzumab 6mg/kg from Day 1 of Cycle 2 to Day 1 of Cycle 8</description>
    <arm_group_label>Trastuzumab and Letrozole</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>- Daily letrozole 2.5 mg/day for 24 weeks</description>
    <arm_group_label>Trastuzumab and Letrozole</arm_group_label>
    <other_name>Femara</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Invasive cancer (clinical stage IB-IIIC)&#xD;
&#xD;
          -  Measurable tumor larger than 1cm&#xD;
&#xD;
          -  ECOG status 0 or 1&#xD;
&#xD;
          -  Postmenopausal women&#xD;
&#xD;
               -  Age ≥55 years and amenorrhea&#xD;
&#xD;
               -  Age &lt;55 years and amenorrhea for ≥12 months with FSH &gt;30 mIU/ml&#xD;
&#xD;
          -  HER2 positive tumor&#xD;
&#xD;
               -  3 positive on IHC&#xD;
&#xD;
               -  2 positive on IHC with HER2 gene amplification on FISH or SISH using a&#xD;
                  single-probe or dual-probe&#xD;
&#xD;
          -  Estrogen receptor positive tumor&#xD;
&#xD;
               -  Positive ER expression with Allred score more than PS3/TS8 or modified Allred&#xD;
                  score more than PS4/TS7&#xD;
&#xD;
          -  Eligible cardiac function&#xD;
&#xD;
               -  Normal heard evaluated by ECG&#xD;
&#xD;
                    -  Consider clinically non-significant arrythmia and ischemic change as normal&#xD;
&#xD;
               -  LVEF ≥ 55% measured by ECHO or MUGA scan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inflammatory breast cancer&#xD;
&#xD;
          -  Bilateral breast cancer&#xD;
&#xD;
          -  Patients with previous breast cancer history&#xD;
&#xD;
          -  Patients with previous breast cancer treatment: Generally include hormone therapy,&#xD;
             chemotherapy, and radiotherapy)&#xD;
&#xD;
          -  Patients having uncontrolled heart problems&#xD;
&#xD;
               -  Ischemic heart disease within 6 months&#xD;
&#xD;
               -  Congestive heart failure more than NYHA class II&#xD;
&#xD;
               -  Unstable angina&#xD;
&#xD;
               -  Clinically significant pericarditis&#xD;
&#xD;
               -  Amyloid heart disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joon Jeong, M.D.,Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gangnam Severance Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joon Jeong, M.D.,Ph.D.</last_name>
    <phone>82220193370</phone>
    <email>gsjjoon@yuhs.ac</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sung Gwe Ahn, M.D.</last_name>
    <phone>82220194402</phone>
    <email>asg2004@yuhs.ac</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hallym University Sacred Heart Hospital</name>
      <address>
        <city>Anyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lee Su Kim, M.D.,Ph.D.</last_name>
      <email>lskim0503@hallym.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inje University Pusan Paik Hospital</name>
      <address>
        <city>Busan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Taehyun Kim, M.D.,Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dankook University Hospital</name>
      <address>
        <city>Cheonan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Junwon Min, M.D.,Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ilsan Paik Hospital</name>
      <address>
        <city>Goyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jae Il Kim, M.D., Ph.D.</last_name>
      <email>erythrokim@paik.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Eun Sook Lee, M.D.,Ph.D.</last_name>
      <email>eslee@ncc.re.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gangnam Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>135720</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joon Jeong, M.D.,Ph.D.</last_name>
      <phone>82220193370</phone>
      <email>gsjjoon@yuhs.ac</email>
    </contact>
    <contact_backup>
      <last_name>Sung Gwe Ahn, M.D.</last_name>
      <phone>82220193370</phone>
      <email>asg2004@yuhs.ac</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Byung Ho Son, M.D.,Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kangbuk Samsung Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chan Heun Park, M.D.,Ph.D.</last_name>
      <email>chanheun.park@samsung.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea Institute of Radiological and Medical Sciences</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Woo Chul Noh, M.D.,Ph.D.</last_name>
      <phone>8229701280</phone>
      <email>nohwoo@kcch.re.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeoung Won Bae, M.D.,Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Seok Jin Nam, M.D.,Ph.D.</last_name>
      <email>seokjin.nam@samsung.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dong Hui Cho</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wonshik Han, M.D.,Ph.D.</last_name>
      <email>hanw@snu.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ajou University School of Medicine</name>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yongsik Jung, M.D.,Ph.D.</last_name>
      <email>drjys@ajou.ac.kr</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <last_update_submitted>February 13, 2018</last_update_submitted>
  <last_update_submitted_qc>February 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Gangnam Severance Hospital</investigator_affiliation>
    <investigator_full_name>Joon Jeong</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Breast cancer</keyword>
  <keyword>HER2</keyword>
  <keyword>ER</keyword>
  <keyword>Postmenopausal</keyword>
  <keyword>Trastuzumab</keyword>
  <keyword>Letrozole</keyword>
  <keyword>Neoadjuvant endocrine treatment</keyword>
  <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>Trastuzumab</mesh_term>
    <mesh_term>Letrozole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02214004
org study id: HERAKLES
nct id: NCT02214004
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate whether trastuzumab and letrozole are effective and
      safe in the preoperative treatment for postmenopausal patients with hormone receptor-positive
      and HER2-positive breast cancer.
Eligibility criteria

        -  Ages Eligible for Study: ≥ 20 years

        -  Invasive cancer (clinical stage IB-IIIB)

        -  Measurable tumor larger than 1cm

        -  ECOG status 0 or 1

        -  Postmenopausal women

             -  Age ≥55 years and amenorrhea

             -  Age <55 years and amenorrhea for ≥12 months with FSH >30 mIU/ml

        -  HER2 positive tumor

             -  3 positive on IHC

             -  2 positive on IHC with HER2 gene amplification on FISH or SISH using a single-probe
                or dual-probe

        -  Estrogen receptor positive tumor

             -  Positive ER expression with Allred score more than PS3/TS8 or modified Allred score
                more than PS4/TS7

        -  Eligible cardiac function

             -  Normal heard evaluated by ECG

                  -  Consider clinically non-significant arrythmia and ischemic change as normal

             -  LVEF ≥ 55% measured by ECHO or MUGA scan

      Outcome measures

        -  Primary End-point

             -  The rate of pathologic complete response (pCR)

                  -  No residual invasive cancer in breast

        -  Secondary End-point

             -  Clinical Response Rate

             -  Safety profiles for the preoperative use of concurrent trastuzumab and letrozole

             -  The rate of breast conservative surgery

             -  Total pathologic complete response (tpCR)

                  -  No residual invasive cancer in breast and ipsilateral axilla

             -  Analysis of biomarkers based on baseline specimen and residual tumor

        -  Ki67 expression

        -  cDNA microarray: gene expression profiling

        -  Association between clinical response rate and circulating tumor cells (CTCs)

             -  CTCs are measured by CytoGen (SEOUL, KOREA)"
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The rate of pathologic complete response
time frame: At time of surgery
description: No residual invasive cancer in breast regardless of axilla
measure: Clinical Response Rate
time frame: At time of surgery
description: Clinical response includes complete response, partial response and stable disease.
measure: Safety profiles for the preoperative use of concurrent trastuzumab and letrozole
time frame: Up to 3 months after surgery
description: Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery
measure: The rate of breast conservative surgery
time frame: Up to 3 weeks after surgery
description: The rate of breast conservative surgery among the patients receiving surgery
measure: Total pathologic complete response (tpCR)
time frame: At time of surgery
description: No residual invasive cancer in breast and ipsilateral axilla
measure: Analysis of biomarkers based on baseline specimen and residual tumor
time frame: Baseline and at time of surgery
description: Ki67 expression
cDNA microarray: gene expression profiling
measure: Association between clinical response rate and circulating tumor cells (CTCs)
time frame: Baseline and at time of surgery
description: Association between clinical response rate and circulating tumor cells (CTCs)
: CTCs are measured by CytoGen (SEOUL, KOREA)"
arm group label: Trastuzumab and Letrozole
arm group type: Experimental
description: - Concurrently initiate two drugs on Day 1 of Cycle 1
intervention type: Drug
intervention name: Trastuzumab
description: - Eight times IV administration of trastuzumab per 3 weeks
Trastuzumab 8mg/kg on Day 1 of Cycle 1
Trastuzumab 6mg/kg from Day 1 of Cycle 2 to Day 1 of Cycle 8
arm group label: Trastuzumab and Letrozole
other name: Herceptin
intervention type: Drug
intervention name: Letrozole
description: - Daily letrozole 2.5 mg/day for 24 weeks
arm group label: Trastuzumab and Letrozole
other name: Femara
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joon Jeong, M.D.,Ph.D.
role: Principal Investigator
affiliation: Gangnam Severance Hospital
last name: Joon Jeong, M.D.,Ph.D.
phone: 82220193370
email: gsjjoon@yuhs.ac
last name: Sung Gwe Ahn, M.D.
phone: 82220194402
email: asg2004@yuhs.ac
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Gangnam Severance Hospital
investigator full name: Joon Jeong
investigator title: Professor
mesh term: Breast Neoplasms
mesh term: Trastuzumab
mesh term: Letrozole
sharing ipd: Undecided