xml: <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/NCT05989347</url>
    </required_header>
    <id_info>
      <org_study_id>2000033529</org_study_id>
      <nct_id>NCT05989347</nct_id>
    </id_info>
    <brief_title>Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant With Neoadjuvant Therapy</brief_title>
    <official_title>A Pilot Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant With Neoadjuvant Therapy for Patient With HER2-negative Early-stage Breast Cancer and Hyperinsulinemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Yale University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Yale University</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary objective of the study is to assess metabolic plasma markers of insulin&#xD;
        resistance in patients with early-stage HER2-negative breast cancers receiving dapagliflozin&#xD;
        concomitant with neoadjuvant therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single arm, open label trial that will evaluate changes in plasma markers of&#xD;
        insulin resistance, namely, fasting glucose and insulin, measured as the HOMA-IR score, as&#xD;
        well as the safety of the addition of dapagliflozin to neoadjuvant treatment in&#xD;
        hyperinsulinemic women with newly diagnosed early stage HER2-negative breast cancers who are&#xD;
        candidates for neoadjuvant therapy.&#xD;
  &#xD;
        Hypotheses are: (i) the SGLT2 inhibitor, dapagliflozin, administered concomitantly with&#xD;
        weekly neoadjuvant therapy in hyperinsulinemic women with newly diagnosed HER2-negative&#xD;
        breast cancers will lead to a decrease in fasting plasma insulin and glucose and thus, a&#xD;
        downregulation in downstream insulin signaling in the tumor as measured by Protein kinase B&#xD;
        (PKB)/AKT phosphorylation. (ii) that dapagliflozin can be safely coadministered at full dose&#xD;
        with multiagent chemotherapy or chemo-immunotherapy.&#xD;
  &#xD;
        Routine, standard of care neoadjuvant chemotherapy, with or without immunotherapy, will be&#xD;
        given together with the investigational product. Acceptable chemotherapy regimens include: 1)&#xD;
        weekly paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide&#xD;
        (ddAC) x 4 treatments (ddAC-T; ); 2) pembrolizumab every 3 weeks (Q3W), with carboplatin +&#xD;
        weekly paclitaxel (cycles 1-4) x12 weeks followed by ddAC x 4 treatments (cycles 5-8)&#xD;
        (KEYNOTE-522 regimen; only for participants with stage II-III ER/PR and HER-negative breast&#xD;
        cancer); 3) docetaxel plus cyclophosphamide and 4) docetaxel plus carboplatin.&#xD;
  &#xD;
        The primary objective of the study is to assess metabolic plasma markers of insulin&#xD;
        resistance in participants with early-stage HER2-negative breast cancers receiving&#xD;
        dapagliflozin concomitant with neoadjuvant therapy.&#xD;
  &#xD;
        Secondary objectives are to: (i) assess changes in the levels of additional plasma markers of&#xD;
        insulin signaling from baseline (before treatment), to during (on-treatment) and immediately&#xD;
        after neoadjuvant therapy (post-treatment), and (ii) assess tissue expression of insulin&#xD;
        signaling intermediates and SGLT2 by immunohistochemistry (IHC) on pre- on- and&#xD;
        post-treatment tissue samples.&#xD;
  &#xD;
        Outcomes will be assessed before treament and 12 weeks post treatment (after completion of&#xD;
        all neoadjuvant therapy but before surgery).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>Phase 1</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>
      <intervention_model_description>Women with BMI ≥ 25 kg/m2 and hyperinsulinemia (HOMA-IR ≥ 2.5) and early stage, operable HER2-negative (by FISH or IHC 0, 1+ or 2+) breast cancer for whom systemic neoadjuvant chemotherapy is indicated.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Change in HOMA-IR (calculated as fasting insulin (μU/ml) x fasting glucose (mmol/l) divided by 22.5.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Fasting glucose</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Fasting plasma glucose measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Fasting insulin</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Fasting plasma insulin measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Insulin-like growth factor-1 (IGF-1)</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Plasma IGF-1 measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Hemoglobin A1c</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Plasma hemoglobin A1c measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Leptin</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Plasma Leptin measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Adiponectin</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Plasma Adiponectin measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Beta-hydroxybuterate</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Plasma Beta-hydroxybuterate measurements will be assessed at baseline and 12 weeks post treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total and phosphorylated PKB/AKT</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Immunohistochemistry (IHC) staining for expression of Total and phosphorylated PKB/AKT in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total and phosphorylated insulin receptor</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin receptor in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R)</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R) in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total and phosphorylated insulin receptor substrate (IRS) 1</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin receptor substrate (IRS) 1 in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sodium-glucose cotransporter-2 (SGLT2)</measure>
      <time_frame>baseline and week 12 post treatment</time_frame>
      <description>Immunohistochemistry (IHC) staining for expression of SGLT2 in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Breast Cancer</condition>
    <condition>Hyperinsulinism</condition>
    <condition>HER2-negative Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Dapagliflozin</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All participants (with insulin resistance and Estrogen Receptor (ER)+HER2-negative or ER/Progesterone receptor (PR)/HER2-negative breast cancer) will receive current standard of care neoadjuvant chemotherapy as determined by the treating physician, plus dapagliflozin 10 mg orally taken daily throughout chemotherapy treatment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dapagliflozin 10mg</intervention_name>
      <description>10 mg tablets for oral administration daily throughout chemotherapy treatment</description>
      <arm_group_label>Dapagliflozin</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Women with newly diagnosed, histologically confirmed, clinical stage I-III,&#xD;
               HER2-negative, invasive breast cancer as defined by ASCO CAP guidelines for whom&#xD;
               neoadjuvant chemotherapy would be indicated. The following chemotherapy regimens are&#xD;
               acceptable&#xD;
  &#xD;
                 1. Weekly paclitaxel, followed by dose dense doxorubicin plus cyclophosphamide&#xD;
  &#xD;
                 2. Docetaxel plus cyclophosphamide&#xD;
  &#xD;
                 3. Docetaxel plus carboplatin&#xD;
  &#xD;
                 4. Paclitaxel plus carboplatin concurrent with every 3 week pembrolizumab followed&#xD;
                    by dose dense doxorubicin plus cyclophosphamide concurrent with every 3 week&#xD;
                    pembrolizumab (KEYNOTE-522 regimen; only for participants with triple negative&#xD;
                    breast cancer)&#xD;
  &#xD;
            -  BMI ≥ 25 kg/m2&#xD;
  &#xD;
            -  Hyperinsulinemia defined as HOMA-IR ≥ 2.5.&#xD;
  &#xD;
            -  Willing and able to provide written informed consent/assent for the trial.&#xD;
  &#xD;
            -  Has sufficient archival breast cancer tissue available from the diagnostic biopsy OR&#xD;
               if not, is willing to undergo a baseline core needle ultrasound guided breast research&#xD;
               biopsy for biomarker analysis prior to day 1 of study.&#xD;
  &#xD;
            -  Willing to undergo an on-treatment research tumor biopsy after 12 weeks of treatment.&#xD;
  &#xD;
            -  Female participants of childbearing potential should have a negative urine or serum&#xD;
               pregnancy within 72 hours prior to receiving the first dose of study medication given&#xD;
               that all participants will be receiving cytotoxic chemotherapy as part of the&#xD;
               treatment regimen, the effects of which can be harmful for the developing fetus. If&#xD;
               the urine test is positive or cannot be confirmed as negative, a serum pregnancy test&#xD;
               will be required.&#xD;
  &#xD;
            -  All participants of childbearing potential should be willing to use 2 methods of birth&#xD;
               control or be surgically sterile or abstain from heterosexual activity for the course&#xD;
               of the study through 120 days after the last dose of study medication.&#xD;
               Non-childbearing potential in women is defined as postmenopausal status without menses&#xD;
               for at least 1 year and an FSH value in the postmenopausal range and/or status post&#xD;
               hysterectomy, oophorectomy or tubal ligation.&#xD;
  &#xD;
            -  Participants should have adequate organ function to tolerate chemotherapy, as defined&#xD;
               by:&#xD;
  &#xD;
                 1. peripheral granulocyte count of &gt; 1,500/mm3&#xD;
  &#xD;
                 2. platelet count &gt; 100,000/mm3&#xD;
  &#xD;
                 3. hemoglobin &gt;9 g/dL&#xD;
  &#xD;
                 4. total bilirubin &lt; 1.5 x upper limit of normal (ULN)&#xD;
  &#xD;
                 5. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each &lt; 1.5 x&#xD;
                    ULN&#xD;
  &#xD;
                 6. serum creatinine &lt; 1.5 x ULN&#xD;
  &#xD;
                 7. INR/PT/PTT each &lt; 1.5 x ULN&#xD;
  &#xD;
            -  Able to swallow oral formulation of the study agent&#xD;
  &#xD;
            -  Subjects should not donate blood while participating in this study, or for at least 90&#xD;
               days following the last dose of chemotherapy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participants who underwent partial excisional biopsy or lumpectomy, segmental&#xD;
               mastectomy or modified radical mastectomy or sentinel node biopsy and therefore cannot&#xD;
               be assessed accurately for pathologic response, are not eligible.&#xD;
  &#xD;
            -  Participants currently pregnant or breastfeeding.&#xD;
  &#xD;
            -  Participants for whom any of the planned chemotherapies are contraindicated.&#xD;
  &#xD;
            -  Participants with currently diagnosed type I or II diabetes mellitus.&#xD;
  &#xD;
            -  Participants taking any antidiabetic medication that would affect insulin resistance&#xD;
               or hyperinsulinemia (i.e. TZD, GLP-1RA, DPP-4i, SGLT2i, metformin) in the past one&#xD;
               month.&#xD;
  &#xD;
            -  Participants with history of hypersensitivity reaction to dapagliflozin.&#xD;
  &#xD;
            -  Participants with eGFR &lt; 25.&#xD;
  &#xD;
            -  History of recurrent (three or more occurrences within 12 months, or two or more&#xD;
               occurrences within 6 months) urinary tract infections.&#xD;
  &#xD;
            -  Currently participating in weight loss programs or weight change in the past 3 months&#xD;
               (&gt; 5% current body weight) or have a history of gastrointestinal surgery.&#xD;
  &#xD;
            -  Live vaccines within 30 days prior to the first dose of trial treatment and while&#xD;
               participating in the trial. Examples of live vaccines include, but are not limited to,&#xD;
               the following: measles, mumps, rubella, chicken pox, yellow fever, intranasal&#xD;
               influenza, rabies, BCG, and typhoid vaccine.&#xD;
  &#xD;
            -  Judgement by the investigator that the participant should not participate in the study&#xD;
               if the participant is unlikely to comply with study procedures, restrictions, and&#xD;
               requirements.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Maryam Lustberg, MD, MPH</last_name>
      <role>Principal Investigator</role>
      <affiliation>Yale University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Adam Blanchard, MS</last_name>
      <phone>(203) 499-9297</phone>
      <email>adam.blanchard@yale.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Yale Cancer Center Smilow Cancer Hospital</name>
        <address>
          <city>New Haven</city>
          <state>Connecticut</state>
          <zip>06520</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 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>
      <mesh_term>Hyperinsulinism</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dapagliflozin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05989347
  org study id: 2000033529
  nct id: NCT05989347
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary objective of the study is to assess metabolic plasma markers of insulin
        resistance in patients with early-stage HER2-negative breast cancers receiving dapagliflozin
        concomitant with neoadjuvant therapy.
  This is a single arm, open label trial that will evaluate changes in plasma markers of
        insulin resistance, namely, fasting glucose and insulin, measured as the HOMA-IR score, as
        well as the safety of the addition of dapagliflozin to neoadjuvant treatment in
        hyperinsulinemic women with newly diagnosed early stage HER2-negative breast cancers who are
        candidates for neoadjuvant therapy.
  
        Hypotheses are: (i) the SGLT2 inhibitor, dapagliflozin, administered concomitantly with
        weekly neoadjuvant therapy in hyperinsulinemic women with newly diagnosed HER2-negative
        breast cancers will lead to a decrease in fasting plasma insulin and glucose and thus, a
        downregulation in downstream insulin signaling in the tumor as measured by Protein kinase B
        (PKB)/AKT phosphorylation. (ii) that dapagliflozin can be safely coadministered at full dose
        with multiagent chemotherapy or chemo-immunotherapy.
  
        Routine, standard of care neoadjuvant chemotherapy, with or without immunotherapy, will be
        given together with the investigational product. Acceptable chemotherapy regimens include: 1)
        weekly paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide
        (ddAC) x 4 treatments (ddAC-T; ); 2) pembrolizumab every 3 weeks (Q3W), with carboplatin +
        weekly paclitaxel (cycles 1-4) x12 weeks followed by ddAC x 4 treatments (cycles 5-8)
        (KEYNOTE-522 regimen; only for participants with stage II-III ER/PR and HER-negative breast
        cancer); 3) docetaxel plus cyclophosphamide and 4) docetaxel plus carboplatin.
  
        The primary objective of the study is to assess metabolic plasma markers of insulin
        resistance in participants with early-stage HER2-negative breast cancers receiving
        dapagliflozin concomitant with neoadjuvant therapy.
  
        Secondary objectives are to: (i) assess changes in the levels of additional plasma markers of
        insulin signaling from baseline (before treatment), to during (on-treatment) and immediately
        after neoadjuvant therapy (post-treatment), and (ii) assess tissue expression of insulin
        signaling intermediates and SGLT2 by immunohistochemistry (IHC) on pre- on- and
        post-treatment tissue samples.
  
        Outcomes will be assessed before treament and 12 weeks post treatment (after completion of
        all neoadjuvant therapy but before surgery).
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Women with BMI ≥ 25 kg/m2 and hyperinsulinemia (HOMA-IR ≥ 2.5) and early stage, operable HER2-negative (by FISH or IHC 0, 1+ or 2+) breast cancer for whom systemic neoadjuvant chemotherapy is indicated.
  primary purpose: Other
  masking: None (Open Label)
  measure: Change in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
  time frame: baseline and week 12 post treatment
  description: Change in HOMA-IR (calculated as fasting insulin (μU/ml) x fasting glucose (mmol/l) divided by 22.5.
  measure: Change in Fasting glucose
  time frame: baseline and week 12 post treatment
  description: Fasting plasma glucose measurements will be assessed at baseline and 12 weeks post treatment
  measure: Change in Fasting insulin
  time frame: baseline and week 12 post treatment
  description: Fasting plasma insulin measurements will be assessed at baseline and 12 weeks post treatment
  measure: Change in Insulin-like growth factor-1 (IGF-1)
  time frame: baseline and week 12 post treatment
  description: Plasma IGF-1 measurements will be assessed at baseline and 12 weeks post treatment
  measure: Change in Hemoglobin A1c
  time frame: baseline and week 12 post treatment
  description: Plasma hemoglobin A1c measurements will be assessed at baseline and 12 weeks post treatment
  measure: Change in Leptin
  time frame: baseline and week 12 post treatment
  description: Plasma Leptin measurements will be assessed at baseline and 12 weeks post treatment
  measure: Change in Adiponectin
  time frame: baseline and week 12 post treatment
  description: Plasma Adiponectin measurements will be assessed at baseline and 12 weeks post treatment
  measure: Change in Beta-hydroxybuterate
  time frame: baseline and week 12 post treatment
  description: Plasma Beta-hydroxybuterate measurements will be assessed at baseline and 12 weeks post treatment
  measure: Total and phosphorylated PKB/AKT
  time frame: baseline and week 12 post treatment
  description: Immunohistochemistry (IHC) staining for expression of Total and phosphorylated PKB/AKT in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
  measure: Total and phosphorylated insulin receptor
  time frame: baseline and week 12 post treatment
  description: Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin receptor in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
  measure: Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R)
  time frame: baseline and week 12 post treatment
  description: Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R) in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
  measure: Total and phosphorylated insulin receptor substrate (IRS) 1
  time frame: baseline and week 12 post treatment
  description: Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin receptor substrate (IRS) 1 in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
  measure: Sodium-glucose cotransporter-2 (SGLT2)
  time frame: baseline and week 12 post treatment
  description: Immunohistochemistry (IHC) staining for expression of SGLT2 in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
  arm group label: Dapagliflozin
  arm group type: Experimental
  description: All participants (with insulin resistance and Estrogen Receptor (ER)+HER2-negative or ER/Progesterone receptor (PR)/HER2-negative breast cancer) will receive current standard of care neoadjuvant chemotherapy as determined by the treating physician, plus dapagliflozin 10 mg orally taken daily throughout chemotherapy treatment.
  intervention type: Drug
  intervention name: Dapagliflozin 10mg
  description: 10 mg tablets for oral administration daily throughout chemotherapy treatment
  arm group label: Dapagliflozin
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Maryam Lustberg, MD, MPH
  role: Principal Investigator
  affiliation: Yale University
  last name: Adam Blanchard, MS
  phone: (203) 499-9297
  email: adam.blanchard@yale.edu
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Hyperinsulinism
  mesh term: Dapagliflozin
  sharing ipd: No