<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/NCT03769415</url>
  </required_header>
  <id_info>
    <org_study_id>LCCC1829</org_study_id>
    <nct_id>NCT03769415</nct_id>
  </id_info>
  <brief_title>Harnessing Analysis RNA Expression and Molecular Subtype to Optimize Novel TherapY MBCA</brief_title>
  <acronym>HARMONY</acronym>
  <official_title>HARMONY: Harnessing the Analysis of RNA Expression and Molecular Subtype to Optimize Novel TherapY for Metastatic Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNC Lineberger Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Veracyte, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>UNC Lineberger Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The HARMONY trial is an interventional trial enrolling metastatic breast cancer (MBC).&#xD;
      Current treatment of breast cancer uses clinical subtype information (e.g. hormone&#xD;
      receptor-positive (HR+)) to help guide treatment options. Breast cancer can also be&#xD;
      characterized by molecular subtype, but it is not known if this information is helpful in&#xD;
      determining treatment when breast cancer has become metastatic. HARMONY will give the&#xD;
      treating physician of each participant the molecular subtype of the tumor based on PAM50&#xD;
      testing. The usefulness of this information will be determined through the physician survey.&#xD;
      Finding out the molecular subtype of each tumor also allows the investigators to determine if&#xD;
      the molecular subtype is different from what is expected based on the clinical subtype. This&#xD;
      study will help determine how new types of information about tumors can help choose&#xD;
      treatments for MBC&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
        1. To determine if clinical: molecular subtypes differ from expected results 15% of the&#xD;
           time&#xD;
&#xD;
        2. To determine if molecular information alters treatment plans, as perceived by treating&#xD;
           physicians through the survey.&#xD;
&#xD;
      Subjects will be consented to the trial and archival tissue from the primary tumor will be&#xD;
      obtained. Stored tissue from metastatic sites will also be obtained. The physician will be&#xD;
      asked what the preferred medications are for the next two lines of treatment. PAM50 testing&#xD;
      to determine molecular subtypes will be determined on primary and metastatic tissue. The&#xD;
      molecular subtype results of the primary tissue will be returned to the physician, and the&#xD;
      physician will again be asked the preferred medications for the next two lines of treatment.&#xD;
      The number of times these medications change between the first and second surveys will be&#xD;
      determined.&#xD;
&#xD;
      Subjects' active participation will only last as long as the consent process.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 6, 2018</start_date>
  <completion_date type="Anticipated">December 15, 2030</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2030</primary_completion_date>
  <phase>N/A</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>Change of treatment plan based on physician survey</measure>
    <time_frame>4 years</time_frame>
    <description>Number of times physicians change response to the question:&quot; What are the preferred next 2 lines of treatment?&quot; after knowledge of molecular subtype</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall rate of clinical:molecular primary tumor subtype incongruence</measure>
    <time_frame>4 years</time_frame>
    <description>Number of times RNA-based molecular subtype differs from clinically determined subtype in primary breast tumors</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intra-patient PFS ratio comparison</measure>
    <time_frame>4 years</time_frame>
    <description>Number of days between initiation of therapy for each line and the date of progression or death (PFS) with adjustment for the expected PFS deterioration over lines of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-patient PFS ratio separated by clinical subtype</measure>
    <time_frame>4 years</time_frame>
    <description>Number of days between initiation of therapy for each line and the date of progression or death (PFS) with adjustment for the expected PFS deterioration over lines of therapy separated by each of the follow clinical subtypes: or HR+/HER2-, HR-/HER2+, HR+/HER2+ and HR-/HER2-</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with HR+/HER2- MBC receiving endocrine therapy on each line of therapy</measure>
    <time_frame>4 years</time_frame>
    <description>Number of patients with HR+/HER2- MBC receiving endocrine therapy based on medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of molecular discordance</measure>
    <time_frame>4 year</time_frame>
    <description>Number of times molecular subtypes determined from primary tissue and molecular subtype determine from metastatic tissue are different</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS comparison in concordant therapy</measure>
    <time_frame>4 years</time_frame>
    <description>PFS for patients receiving clinically-concordant therapy .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS comparison in disconcordant therapy</measure>
    <time_frame>4 years</time_frame>
    <description>PFS for patients receiving clinically-discordant therapy in congruent tumors</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Intrinsic subtyping of Primary Breast Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intrinsic subtype of primary breast tissue from metastatic breast cancer subject will be determined</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Intrinsic Subtyping of Primary Breast Cancer</intervention_name>
    <description>Primary breast tissue will be sent for Nanostring PAM50 Testing to determine intrinsic subtype</description>
    <arm_group_label>Intrinsic subtyping of Primary Breast Cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women or men at least 18 years of age&#xD;
&#xD;
          -  Pathologically documented diagnosis of measurable or evaluable metastatic breast&#xD;
             cancer with known ER, PR, and HER2 status determined by the local laboratory on the&#xD;
             primary tumor.&#xD;
&#xD;
          -  Enrolled before or during first line of treatment for metastatic breast cancer. No&#xD;
             more than 1 prior line of therapy in the metastatic setting.&#xD;
&#xD;
          -  Accessible medical records for all treatment and response data in the metastatic&#xD;
             setting.&#xD;
&#xD;
          -  Willing and able to receive medical treatment or follow up by investigators at&#xD;
             UNC-Chapel Hill.&#xD;
&#xD;
          -  Receiving treatment for metastatic breast cancer.&#xD;
&#xD;
          -  Treating physician considers patient well enough for standard of care therapy&#xD;
             including chemotherapy.&#xD;
&#xD;
          -  Willing to give blood for research purposes upon study enrollment and at first disease&#xD;
             progression.&#xD;
&#xD;
          -  Available archival primary tumor suitable for molecular analysis. If the primary is&#xD;
             not available, willingness to obtain extra samples for research during planned&#xD;
             standard of care biopsy, or willingness to undergo biopsy for repeat clinical&#xD;
             receptors and molecular analyses.&#xD;
&#xD;
          -  Archival metastatic sample available and suitable for molecular analysis. If not&#xD;
             available, willingness to undergo biopsy for repeat clinical receptors and molecular&#xD;
             analyses. If no archival metastatic sample is available and the metastasis is not&#xD;
             amenable to biopsy per treating physician the patient may still be enrolled.&#xD;
&#xD;
          -  Be willing and capable of providing informed consent, recognize the experimental&#xD;
             nature of the trial, and sign the IRB-approved written informed consent documentations&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Does not have tissue available or suitable for molecular analysis, or is unwilling to&#xD;
             provide tissue for research at the time of a clinically indicated procedure.&#xD;
&#xD;
          -  Has dementia, altered mental status, or any psychiatric or co-morbid condition&#xD;
             prohibiting the understanding or rending of informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisa A Carey, MD, FASCO, ScM</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNC Lineberger Comprehensive Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Michele A Hayward</last_name>
    <phone>919-966-9259</phone>
    <email>michele_hayward@med.unc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Erin Kelly</last_name>
    <phone>919-966-0040</phone>
    <email>erin_kelly@med.unc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rebekah Craver</last_name>
      <phone>919-966-7490</phone>
      <email>Rebekah_Craver@med.unc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Terri Eubanks</last_name>
      <phone>9199664530</phone>
      <email>teubanks@med.unc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Lisa A Carey, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UNC Rex Healthcare</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tamiko Myatt</last_name>
      <phone>919-784-2500</phone>
      <email>Tamiko.Myatt@unchealth.unc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Terri A Eubanks</last_name>
      <phone>919-966-4530</phone>
      <email>teubanks@med.unc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>JoEllen Speca</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://unclineberger.org/patientcare/clinical-trials/clinical-trials</url>
    <description>Clinical trials at UNC Lineberger</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</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>
  <!-- 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/NCT03769415
org study id: LCCC1829
nct id: NCT03769415
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The HARMONY trial is an interventional trial enrolling metastatic breast cancer (MBC).
      Current treatment of breast cancer uses clinical subtype information (e.g. hormone
      receptor-positive (HR+)) to help guide treatment options. Breast cancer can also be
      characterized by molecular subtype, but it is not known if this information is helpful in
      determining treatment when breast cancer has become metastatic. HARMONY will give the
      treating physician of each participant the molecular subtype of the tumor based on PAM50
      testing. The usefulness of this information will be determined through the physician survey.
      Finding out the molecular subtype of each tumor also allows the investigators to determine if
      the molecular subtype is different from what is expected based on the clinical subtype. This
      study will help determine how new types of information about tumors can help choose
      treatments for MBC
Primary Objectives:

        1. To determine if clinical: molecular subtypes differ from expected results 15% of the
           time

        2. To determine if molecular information alters treatment plans, as perceived by treating
           physicians through the survey.

      Subjects will be consented to the trial and archival tissue from the primary tumor will be
      obtained. Stored tissue from metastatic sites will also be obtained. The physician will be
      asked what the preferred medications are for the next two lines of treatment. PAM50 testing
      to determine molecular subtypes will be determined on primary and metastatic tissue. The
      molecular subtype results of the primary tissue will be returned to the physician, and the
      physician will again be asked the preferred medications for the next two lines of treatment.
      The number of times these medications change between the first and second surveys will be
      determined.

      Subjects' active participation will only last as long as the consent process.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change of treatment plan based on physician survey
time frame: 4 years
description: Number of times physicians change response to the question:" What are the preferred next 2 lines of treatment?" after knowledge of molecular subtype
measure: Overall rate of clinical:molecular primary tumor subtype incongruence
time frame: 4 years
description: Number of times RNA-based molecular subtype differs from clinically determined subtype in primary breast tumors
measure: Intra-patient PFS ratio comparison
time frame: 4 years
description: Number of days between initiation of therapy for each line and the date of progression or death (PFS) with adjustment for the expected PFS deterioration over lines of therapy
measure: Intra-patient PFS ratio separated by clinical subtype
time frame: 4 years
description: Number of days between initiation of therapy for each line and the date of progression or death (PFS) with adjustment for the expected PFS deterioration over lines of therapy separated by each of the follow clinical subtypes: or HR+/HER2-, HR-/HER2+, HR+/HER2+ and HR-/HER2-
measure: Number of patients with HR+/HER2- MBC receiving endocrine therapy on each line of therapy
time frame: 4 years
description: Number of patients with HR+/HER2- MBC receiving endocrine therapy based on medical record
measure: Rate of molecular discordance
time frame: 4 year
description: Number of times molecular subtypes determined from primary tissue and molecular subtype determine from metastatic tissue are different
measure: PFS comparison in concordant therapy
time frame: 4 years
description: PFS for patients receiving clinically-concordant therapy .
measure: PFS comparison in disconcordant therapy
time frame: 4 years
description: PFS for patients receiving clinically-discordant therapy in congruent tumors
arm group label: Intrinsic subtyping of Primary Breast Cancer
arm group type: Experimental
description: Intrinsic subtype of primary breast tissue from metastatic breast cancer subject will be determined
intervention type: Device
intervention name: Intrinsic Subtyping of Primary Breast Cancer
description: Primary breast tissue will be sent for Nanostring PAM50 Testing to determine intrinsic subtype
arm group label: Intrinsic subtyping of Primary Breast Cancer
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Lisa A Carey, MD, FASCO, ScM
role: Principal Investigator
affiliation: UNC Lineberger Comprehensive Cancer Center
last name: Michele A Hayward
phone: 919-966-9259
email: michele_hayward@med.unc.edu
last name: Erin Kelly
phone: 919-966-0040
email: erin_kelly@med.unc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
url: http://unclineberger.org/patientcare/clinical-trials/clinical-trials
description: Clinical trials at UNC Lineberger
responsible party type: Sponsor
mesh term: Breast Neoplasms