<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/NCT01666171</url>
  </required_header>
  <id_info>
    <org_study_id>CALGB-A211201</org_study_id>
    <secondary_id>CDR0000738328</secondary_id>
    <nct_id>NCT01666171</nct_id>
  </id_info>
  <brief_title>Studying Changes in Breast Density in Patients With Early-Stage Breast Cancer Treated With Metformin Hydrochloride or Placebo on CAN-NCIC-MA.32</brief_title>
  <official_title>Change in Mammographic Density With Metformin Use: A Companion Study to NCIC Study MA.32</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer and Leukemia Group B</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <brief_summary>
    <textblock>
      RATIONALE: Learning about the effect of metformin hydrochloride in breast density of women&#xD;
      with early-stage breast cancer may help plan treatment.&#xD;
&#xD;
      PURPOSE: This trial studies changes in breast density in patients with early-stage breast&#xD;
      cancer treated with metformin hydrochloride or placebo on CAN-NCIC-MA.32.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES:&#xD;
&#xD;
      Primary&#xD;
&#xD;
        -  To evaluate the change in percent mammographic density in contralateral (unaffected&#xD;
           breast) from prior to the initiation of metformin hydrochloride (metformin) or placebo&#xD;
           treatment through one year of therapy in patients with hormone receptor-negative breast&#xD;
           cancer (i.e., not on endocrine therapy).&#xD;
&#xD;
      Secondary&#xD;
&#xD;
        -  To evaluate the change in percent breast density in contralateral (unaffected breast)&#xD;
           from prior to the initiation of metformin or placebo treatment through two years of&#xD;
           therapy in patients with hormone receptor-negative breast cancer (i.e., not on endocrine&#xD;
           therapy).&#xD;
&#xD;
        -  To evaluate whether baseline mammographic density correlates with baseline of fasting&#xD;
           plasma insulin, glucose levels, and Homeostasis Model Assessment (HOMA) (collected on&#xD;
           the treatment protocol CAN-NCIC-MA.32) (MA.32).&#xD;
&#xD;
        -  To evaluate whether changes in dense area in response to metformin therapy from&#xD;
           pre-treatment through two years of therapy correlate with changes in fasting plasma&#xD;
           insulin, glucose levels, and HOMA (collected on the treatment protocol MA.32) over the&#xD;
           same time period.&#xD;
&#xD;
        -  To explore whether change in mammographic density for women on metformin is associated&#xD;
           with risk of second primary breast cancer.&#xD;
&#xD;
      OUTLINE: Patients' mammograms taken at baseline and at approximately 1 and 2 years of&#xD;
      metformin or placebo treatment are retrieved and analyzed for breast-density change.&#xD;
      Pre-menopausal patients' menstrual cycle information is also collected at baseline and every&#xD;
      6 months for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <primary_completion_date type="Anticipated">April 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <primary_outcome>
    <measure>Change in percent mammographic breast density in contralateral (unaffected) breast from baseline to 1 year using two-sample t-test or Wilcoxon rank-sum test</measure>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in percent mammographic breast density in contralateral (unaffected) breast from baseline to 2 years using two-sample t-test</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between baseline mammographic density and baseline plasma fasting insulin, glucose levels, and HOMA using a scatter plot, correlation-coefficient estimation, and linear-regression method</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of changes in dense area in response to metformin therapy from pre-treatment to on treatment (at year 1 and year 2) with plasma fasting insulin, glucose levels, and HOMA using simple linear-regression method</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between mammographic density and the incidence of second primary breast cancer using correlation coefficient and scatter plot</measure>
  </secondary_outcome>
  <enrollment type="Anticipated">458</enrollment>
  <condition>Breast Cancer</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin hydrochloride</intervention_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>clinical observation</intervention_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>diagnostic laboratory biomarker analysis</intervention_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>imaging biomarker analysis</intervention_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>medical chart review</intervention_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>digital mammography</intervention_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        DISEASE CHARACTERISTICS:&#xD;
&#xD;
          -  Patients must either be concurrently enrolling or previously enrolled to Canada (CAN)&#xD;
             National Cancer Institute of Canada (NCIC) study MA.32 (CAN-NCIC-MA.32) (MA.32);&#xD;
             eligible patients may be either pre- or post-menopausal&#xD;
&#xD;
          -  Patients must have hormone receptor-negative breast cancer&#xD;
&#xD;
          -  Patients must have breast density ≥ 25% (correlating with the Breast Imaging-Reporting&#xD;
             and Data [BIRAD]-2 category of &quot;scattered fibroglandular densities&quot; or greater)&#xD;
&#xD;
          -  Baseline digital mammograms taken within 12 months prior to registration to MA.32,&#xD;
             with at least a craniocaudal (CC) view used for enrollment to MA.32 must be available&#xD;
             for submission; if the patient has previously enrolled to MA.32 and one year has&#xD;
             elapsed from baseline mammograms, one-year mammograms must also be available for&#xD;
             submission&#xD;
&#xD;
          -  Contralateral unaffected breast in place (with no prior cancer or radiation, no&#xD;
             implants, and no plan for breast surgery on contralateral breast over the course of&#xD;
             the study); women with a prior biopsy on the unaffected breast are eligible&#xD;
&#xD;
        PATIENT CHARACTERISTICS:&#xD;
&#xD;
          -  Not specified&#xD;
&#xD;
        PRIOR CONCURRENT THERAPY:&#xD;
&#xD;
          -  See Disease Characteristics&#xD;
&#xD;
          -  Women receiving endocrine therapy (e.g., tamoxifen, aromatase inhibitors) are not&#xD;
             eligible&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie E. Wood, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Vermont</affiliation>
  </overall_official>
  <verification_date>January 2013</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>July 9, 2013</last_update_submitted>
  <last_update_submitted_qc>July 9, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 10, 2013</last_update_posted>
  <responsible_party>
    <name_title>Richard L. Schilsky</name_title>
    <organization>Cancer and Leukemia Group B</organization>
  </responsible_party>
  <keyword>estrogen receptor-negative breast cancer</keyword>
  <keyword>progesterone receptor-negative breast cancer</keyword>
  <keyword>stage IB breast cancer</keyword>
  <keyword>stage II breast cancer</keyword>
  <keyword>stage IIIA breast cancer</keyword>
  <keyword>stage IIIC breast cancer</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>
  </intervention_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/NCT01666171
org study id: CALGB-A211201
secondary id: CDR0000738328
nct id: NCT01666171
lead sponsor: 
collaborator: 
RATIONALE: Learning about the effect of metformin hydrochloride in breast density of women
      with early-stage breast cancer may help plan treatment.

      PURPOSE: This trial studies changes in breast density in patients with early-stage breast
      cancer treated with metformin hydrochloride or placebo on CAN-NCIC-MA.32.
OBJECTIVES:

      Primary

        -  To evaluate the change in percent mammographic density in contralateral (unaffected
           breast) from prior to the initiation of metformin hydrochloride (metformin) or placebo
           treatment through one year of therapy in patients with hormone receptor-negative breast
           cancer (i.e., not on endocrine therapy).

      Secondary

        -  To evaluate the change in percent breast density in contralateral (unaffected breast)
           from prior to the initiation of metformin or placebo treatment through two years of
           therapy in patients with hormone receptor-negative breast cancer (i.e., not on endocrine
           therapy).

        -  To evaluate whether baseline mammographic density correlates with baseline of fasting
           plasma insulin, glucose levels, and Homeostasis Model Assessment (HOMA) (collected on
           the treatment protocol CAN-NCIC-MA.32) (MA.32).

        -  To evaluate whether changes in dense area in response to metformin therapy from
           pre-treatment through two years of therapy correlate with changes in fasting plasma
           insulin, glucose levels, and HOMA (collected on the treatment protocol MA.32) over the
           same time period.

        -  To explore whether change in mammographic density for women on metformin is associated
           with risk of second primary breast cancer.

      OUTLINE: Patients' mammograms taken at baseline and at approximately 1 and 2 years of
      metformin or placebo treatment are retrieved and analyzed for breast-density change.
      Pre-menopausal patients' menstrual cycle information is also collected at baseline and every
      6 months for 2 years.
measure: Change in percent mammographic breast density in contralateral (unaffected) breast from baseline to 1 year using two-sample t-test or Wilcoxon rank-sum test
measure: Change in percent mammographic breast density in contralateral (unaffected) breast from baseline to 2 years using two-sample t-test
measure: Correlation between baseline mammographic density and baseline plasma fasting insulin, glucose levels, and HOMA using a scatter plot, correlation-coefficient estimation, and linear-regression method
measure: Correlation of changes in dense area in response to metformin therapy from pre-treatment to on treatment (at year 1 and year 2) with plasma fasting insulin, glucose levels, and HOMA using simple linear-regression method
measure: Correlation between mammographic density and the incidence of second primary breast cancer using correlation coefficient and scatter plot
intervention type: Drug
intervention name: metformin hydrochloride
intervention type: Other
intervention name: clinical observation
intervention type: Other
intervention name: diagnostic laboratory biomarker analysis
intervention type: Other
intervention name: imaging biomarker analysis
intervention type: Other
intervention name: medical chart review
intervention type: Procedure
intervention name: digital mammography
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Marie E. Wood, MD
role: Principal Investigator
affiliation: University of Vermont
name title: Richard L. Schilsky
organization: Cancer and Leukemia Group B
mesh term: Breast Neoplasms
mesh term: Metformin