<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/NCT03238495</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00140673</org_study_id>
    <nct_id>NCT03238495</nct_id>
  </id_info>
  <brief_title>Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer</brief_title>
  <acronym>HERMET</acronym>
  <official_title>Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Qamar Khan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kansas Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the efficacy of metformin as a repurposed&#xD;
      agent in human epidermal growth factor receptor 2 (HER2) positive breast cancer when added to&#xD;
      standard neo-adjuvant chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 15, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2022</primary_completion_date>
  <phase>Phase 2</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>Pathologic complete response (pCR)</measure>
    <time_frame>Up to 6 weeks after last chemotherapy treatment</time_frame>
    <description>pCR at surgery</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>HER2-positive Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Chemotherapy Only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Taxotere, Carboplatin, Herceptin + Pertuzumab (TCH+P)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chemotherapy plus Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TCH+P plus metformin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Taxotere, Carboplatin, Herceptin + Pertuzumab</intervention_name>
    <description>TCH+P chemotherapy every 3 weeks for 6 cycles: Taxotere 75mg/m2, Carboplatin AUC 6, Herceptin 6mg/kg (first cycle loading dose of 8mg/kg), Pertuzumab 420mg (first cycle loading does of 840mg)</description>
    <arm_group_label>Chemotherapy Only</arm_group_label>
    <arm_group_label>Chemotherapy plus Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>TCH+P chemotherapy every 3 weeks for 6 cycles. Metformin 850 mg daily during the first cycle, then 850 mg twice daily for the remaining 5 cycles.</description>
    <arm_group_label>Chemotherapy plus Metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.&#xD;
&#xD;
          -  Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by&#xD;
             needle core biopsy. Fine-needle aspiration is not sufficient. Incisional/excisional&#xD;
             biopsy is not allowed. In case of bilateral cancer, the investigator has to decide&#xD;
             prospectively which side will be evaluated for the primary endpoint.&#xD;
&#xD;
          -  Study participants must be cT1c - cT4a-d, any node (N), no metastases (M0). Any tumor&#xD;
             (T) is allowed if node positive (biopsy proven and HER2 positive) including no primary&#xD;
             invasive cancer or only ductal carcinoma in situ (DCIS). Metastatic workup is not&#xD;
             required.&#xD;
&#xD;
          -  Breast tumor must be &gt;1.5 cm in maximum diameter by clinical or any radiologic&#xD;
             measurement, if node negative. If node is positive by biopsy, study participant will&#xD;
             be eligible regardless of the size of the breast primary. In case of inflammatory&#xD;
             breast cancer, the extent of inflammation/erythema can be used as measurable lesion.&#xD;
&#xD;
          -  Multifocal or multicentric breast cancer is allowed if all the lesions are biopsied&#xD;
             and are HER2 positive. Largest lesion will be assigned the target lesion.&#xD;
&#xD;
          -  Must be HER2-positive in primary breast tumor or lymph node by the ASCO/CAP guidelines&#xD;
             2013: http://www.asco.org/guidelines/her2&#xD;
&#xD;
          -  Ejection fraction (EF) greater than 50% by MUGA or ECHO within 4 weeks prior to first&#xD;
             dose of study treatment.&#xD;
&#xD;
          -  No prior cancer chemotherapy allowed.&#xD;
&#xD;
          -  Adequate organ and marrow function as defined below, unless deemed non-clinically&#xD;
             significant and approved by the Principal Investigator:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  Platelets ≥ 100,000/mcl&#xD;
&#xD;
               -  total bilirubin within normal institutional limits&#xD;
&#xD;
               -  AST(SGOT) ≤ 2.5 X institutional upper limit of normal&#xD;
&#xD;
               -  ALT(SPGT) ≤ 2.5 X institutional upper limit of normal&#xD;
&#xD;
               -  ALK Phos ≤ 2.5 X institutional upper limit of normal&#xD;
&#xD;
               -  Creatinine clearance &gt; 50mL/min&#xD;
&#xD;
          -  Women of child-bearing potential must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry, for the duration of&#xD;
             study participation, and for 90 days following completion of therapy.&#xD;
&#xD;
          -  Negative pregnancy test within 14 days prior to randomization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant, breastfeeding, or unwilling to practice birth control during participation&#xD;
             in the study&#xD;
&#xD;
          -  Presence of a condition or abnormality that in the opinion of the Investigator would&#xD;
             compromise the safety of the study participant or the quality of the study data.&#xD;
&#xD;
          -  Current or anticipated use of other investigational agents.&#xD;
&#xD;
          -  Prior chemotherapy for any malignancy.&#xD;
&#xD;
          -  Prior radiation therapy for breast cancer&#xD;
&#xD;
          -  Previous malignant disease being disease-free for less than 5 years (except carcinoma&#xD;
             in situ (CIS) of the cervix and non-melanoma skin cancer).&#xD;
&#xD;
          -  Patients with diabetes on metformin. Patients with diabetes and not on metformin will&#xD;
             be eligible if it is deemed safe after consultation with the patient physician&#xD;
             managing diabetes.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to metformin or other agents used in study.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#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>Qamar Khan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kansas Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Clinical Trials Nurse Navigator</last_name>
    <phone>913-945-7552</phone>
    <email>ctnursenav@kumc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, West Clinic</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, Westwood Campus</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, Overland Park Clinic</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, South Clinic</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64131</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, North Clinic</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64154</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, Lee's Summit Clinic</name>
      <address>
        <city>Lee's Summit</city>
        <state>Missouri</state>
        <zip>64064</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>December 4, 2021</last_update_submitted>
  <last_update_submitted_qc>December 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kansas Medical Center</investigator_affiliation>
    <investigator_full_name>Qamar Khan</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Operable breast cancer</keyword>
  <keyword>Neo-adjuvant chemotherapy</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>Metformin</mesh_term>
    <mesh_term>Carboplatin</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/NCT03238495
org study id: STUDY00140673
nct id: NCT03238495
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary objective of this study is to determine the efficacy of metformin as a repurposed
      agent in human epidermal growth factor receptor 2 (HER2) positive breast cancer when added to
      standard neo-adjuvant chemotherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic complete response (pCR)
time frame: Up to 6 weeks after last chemotherapy treatment
description: pCR at surgery
arm group label: Chemotherapy Only
arm group type: Active Comparator
description: Taxotere, Carboplatin, Herceptin + Pertuzumab (TCH+P)
arm group label: Chemotherapy plus Metformin
arm group type: Experimental
description: TCH+P plus metformin
intervention type: Drug
intervention name: Taxotere, Carboplatin, Herceptin + Pertuzumab
description: TCH+P chemotherapy every 3 weeks for 6 cycles: Taxotere 75mg/m2, Carboplatin AUC 6, Herceptin 6mg/kg (first cycle loading dose of 8mg/kg), Pertuzumab 420mg (first cycle loading does of 840mg)
arm group label: Chemotherapy Only
arm group label: Chemotherapy plus Metformin
intervention type: Drug
intervention name: Metformin
description: TCH+P chemotherapy every 3 weeks for 6 cycles. Metformin 850 mg daily during the first cycle, then 850 mg twice daily for the remaining 5 cycles.
arm group label: Chemotherapy plus Metformin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Qamar Khan, MD
role: Principal Investigator
affiliation: University of Kansas Medical Center
last name: Clinical Trials Nurse Navigator
phone: 913-945-7552
email: ctnursenav@kumc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kansas Medical Center
investigator full name: Qamar Khan
investigator title: Associate Professor
mesh term: Breast Neoplasms
mesh term: Metformin
mesh term: Carboplatin
mesh term: Docetaxel
mesh term: Trastuzumab
mesh term: Pertuzumab
sharing ipd: No