<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/NCT03303846</url>
  </required_header>
  <id_info>
    <org_study_id>17009</org_study_id>
    <secondary_id>NCI-2017-01757</secondary_id>
    <secondary_id>U01CA189283</secondary_id>
    <nct_id>NCT03303846</nct_id>
  </id_info>
  <brief_title>Combined Breast MRI and Biomarker Strategies in Identifying High-risk Breast Cancer Patients</brief_title>
  <official_title>Combined Breast MRI/Biomarker Strategies to Identify Aggressive Biology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</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>
      This clinical trial studies normal breast tissue changes combined with breast magnetic&#xD;
      resonance imaging (MRI) that may suggest the beginnings of cancer development. Using breast&#xD;
      tissue markers in combination with breast imaging such as MRI may help to more accurately&#xD;
      assess a woman's risk of developing breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the number of high risk women with abnormal screening breast MRI and&#xD;
      morphologically normal biopsy over 7 years.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine if WNT10B/mutant p53 expression as measured in the 0-month biopsy predicts&#xD;
      women with an abnormal MRI/non-cancerous biopsy who will progress to cancer over 7 years.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the predictive accuracy of WNT10B with MRI, of which will be compared with&#xD;
      MRI alone using the C-index.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Participants undergo standard of care high risk breast cancer screening MRIs at baseline and&#xD;
      follow-up and blood sample collection at baseline. Participants undergo collection of breast&#xD;
      tissue samples at any breast biopsy or breast surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2023</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>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of triple-negative breast cancer (invasive and/or ductal carcinoma in situ [DCIS]) within the 12-month period of the study</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Development of breast cancers other than triple-negative (e.g. estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) the study analysis, however they will be reported as descriptive statistics.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Expression of WNT10B/mutant p53 in morphologically normal breast tissue</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Biopsy tissue will be assessed for 1) activated WNT10B (measured by presence of high phospho-beta-catenin; present vs. absent) and 2) loss of p53 function (measured by the loss of p21 expression; present versus [vs.] absent). The optimal cut for the WNT10B to differentiate progression vs. non-progression women will be carried out by receiver operating characteristic (ROC) analysis, and hence WNT10B expression will be dichotomized to high vs. low expression. Chi-square test 12-month progression. Adjusted association will be further explored by logistic regression incorporating subject characteristics, such as age, body mass index (BMI), race, and BRCA1.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Predictive accuracy of WNT10B with magnetic resonance imaging (MRI)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The specificity for MRI combined with WNT10B and/or p53 based biomarkers to detect triple negative breast cancer (TNBC) will be calculated with 95% confidence interval (CI). Its prediction accuracy will be described by C-index and compared to that by diagnosis by MRI alone.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">650</enrollment>
  <condition>Healthy Subject</condition>
  <arm_group>
    <arm_group_label>Treatment (breast MRI, biopsy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants undergo standard of care high risk breast cancer screening MRIs at baseline and follow-up and blood sample collection at baseline. Participants also undergo collection of breast tissue samples at any breast biopsy or breast surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance Imaging</intervention_name>
    <description>Undergo high risk breast cancer screening MRI</description>
    <arm_group_label>Treatment (breast MRI, biopsy)</arm_group_label>
    <other_name>Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
    <other_name>MRI</other_name>
    <other_name>NMR Imaging</other_name>
    <other_name>NMRI</other_name>
    <other_name>Nuclear Magnetic Resonance Imaging</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo blood and tissue sample collection</description>
    <arm_group_label>Treatment (breast MRI, biopsy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (breast MRI, biopsy)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women who are undergoing screening breast MRI as per standard of care for high-risk&#xD;
             breast cancer screening&#xD;
&#xD;
          -  Willing to donate left-over tissue if patient undergoes a breast biopsy and/or breast&#xD;
             surgery&#xD;
&#xD;
          -  Willing to have about 40 mL of blood (approximately 3 tablespoons) drawn&#xD;
&#xD;
          -  Documented informed consent of the participant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy or intolerance to gadolinium&#xD;
&#xD;
          -  Inability to undergo breast MRI (e.g. claustrophobia)&#xD;
&#xD;
          -  Participants with active cancer diagnosis (exception: skin cancer, biopsy-proven&#xD;
             atypical lobular, ductal hyperplasia and/or lobular carcinoma in situ)&#xD;
&#xD;
          -  Previous diagnosis of stage 4 cancer&#xD;
&#xD;
          -  Participants who have received cytotoxic chemotherapy within 1 year prior to screening&#xD;
             breast MRI&#xD;
&#xD;
          -  Participants who have received endocrine therapy within 1 year prior to screening&#xD;
             breast MRI&#xD;
&#xD;
          -  Participants who have received breast radiation within 1 year prior to screening&#xD;
             breast MRI&#xD;
&#xD;
          -  Radiation to both breasts&#xD;
&#xD;
          -  Pregnant and/or lactating within 1 year prior to screening breast MRI&#xD;
&#xD;
          -  Receives screening breast MRIs at an outside facility other than the consenting&#xD;
             institution&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Victoria Seewaldt, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tanya Chavez</last_name>
      <phone>626-218-0634</phone>
      <email>tachavez@coh.org</email>
    </contact>
    <investigator>
      <last_name>Victoria Seewaldt, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lisa Yee, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristy Watkins</last_name>
      <phone>323-865-0452</phone>
      <email>Watkins_K@med.usc.edu</email>
    </contact>
    <investigator>
      <last_name>Julie E. Lang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Gallagher</last_name>
      <phone>919-970-1551</phone>
      <email>jennifer.gallagher@duke.edu</email>
    </contact>
    <investigator>
      <last_name>Terry Hyslop, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ohio State University, Stefanie Spielman Comprehensive Breast Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Woelke</last_name>
      <phone>419-308-4708</phone>
      <email>sarah.woelke@osumc.edu</email>
    </contact>
    <investigator>
      <last_name>Steven K. Clinton, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lisa Yee, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>537192</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Renae Quale</last_name>
      <phone>608-263-7898</phone>
      <email>rmquale@wisc.edu</email>
    </contact>
    <investigator>
      <last_name>Ruth O'Regan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03303846
org study id: 17009
secondary id: NCI-2017-01757
secondary id: U01CA189283
nct id: NCT03303846
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This clinical trial studies normal breast tissue changes combined with breast magnetic
      resonance imaging (MRI) that may suggest the beginnings of cancer development. Using breast
      tissue markers in combination with breast imaging such as MRI may help to more accurately
      assess a woman's risk of developing breast cancer.
PRIMARY OBJECTIVES:

      I. To determine the number of high risk women with abnormal screening breast MRI and
      morphologically normal biopsy over 7 years.

      SECONDARY OBJECTIVES:

      I. To determine if WNT10B/mutant p53 expression as measured in the 0-month biopsy predicts
      women with an abnormal MRI/non-cancerous biopsy who will progress to cancer over 7 years.

      TERTIARY OBJECTIVES:

      I. To determine the predictive accuracy of WNT10B with MRI, of which will be compared with
      MRI alone using the C-index.

      OUTLINE:

      Participants undergo standard of care high risk breast cancer screening MRIs at baseline and
      follow-up and blood sample collection at baseline. Participants undergo collection of breast
      tissue samples at any breast biopsy or breast surgery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Incidence of triple-negative breast cancer (invasive and/or ductal carcinoma in situ [DCIS]) within the 12-month period of the study
time frame: Up to 12 months
description: Development of breast cancers other than triple-negative (e.g. estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) the study analysis, however they will be reported as descriptive statistics.
measure: Expression of WNT10B/mutant p53 in morphologically normal breast tissue
time frame: Up to 12 months
description: Biopsy tissue will be assessed for 1) activated WNT10B (measured by presence of high phospho-beta-catenin; present vs. absent) and 2) loss of p53 function (measured by the loss of p21 expression; present versus [vs.] absent). The optimal cut for the WNT10B to differentiate progression vs. non-progression women will be carried out by receiver operating characteristic (ROC) analysis, and hence WNT10B expression will be dichotomized to high vs. low expression. Chi-square test 12-month progression. Adjusted association will be further explored by logistic regression incorporating subject characteristics, such as age, body mass index (BMI), race, and BRCA1.
measure: Predictive accuracy of WNT10B with magnetic resonance imaging (MRI)
time frame: Up to 12 months
description: The specificity for MRI combined with WNT10B and/or p53 based biomarkers to detect triple negative breast cancer (TNBC) will be calculated with 95% confidence interval (CI). Its prediction accuracy will be described by C-index and compared to that by diagnosis by MRI alone.
arm group label: Treatment (breast MRI, biopsy)
arm group type: Experimental
description: Participants undergo standard of care high risk breast cancer screening MRIs at baseline and follow-up and blood sample collection at baseline. Participants also undergo collection of breast tissue samples at any breast biopsy or breast surgery.
intervention type: Procedure
intervention name: Magnetic Resonance Imaging
description: Undergo high risk breast cancer screening MRI
arm group label: Treatment (breast MRI, biopsy)
other name: Magnetic Resonance / Nuclear Magnetic Resonance
other name: MRI
other name: NMR Imaging
other name: NMRI
other name: Nuclear Magnetic Resonance Imaging
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo blood and tissue sample collection
arm group label: Treatment (breast MRI, biopsy)
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (breast MRI, biopsy)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Victoria Seewaldt, MD
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor