Breast CancerPhase 1NCT05989347
Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant With Neoadjuvant Therapy
A Phase 1 study testing Dapagliflozin 10mg in people with Breast Cancer and Hyperinsulinism, run by Yale University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Hyperinsulinism, HER2-negative Breast Cancer
- What is being tested?
- Dapagliflozin 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2024to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women > 18 years of age with newly diagnosed, histologically confirmed, clinical stage I-III, HER2-negative - either ER+ or triple negative - invasive breast cancer as defined by ASCO CAP guidelines for whom neoadjuvant chemotherapy would be indicated. The following chemotherapy regimens are acceptable:
- Weekly or dose dense paclitaxel, followed by dose dense doxorubicin plus cyclophosphamide
- Docetaxel plus cyclophosphamide
- Docetaxel plus carboplatin plus or minus pembrolizumab
- Paclitaxel plus carboplatin concurrent with every 3 week pembrolizumab followed by dose dense doxorubicin plus cyclophosphamide concurrent with every 3 week pembrolizumab (KEYNOTE-522 regimen; only for participants with triple negative breast cancer)
- BMI ≥ 25 kg/m2
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- Hyperinsulinemia defined as HOMA-IR ≥ 2.5.
- Willing and able to provide written informed consent for the trial.
- Has at least one (1) physical 4-5-micron single H\&E slide from diagnostic biopsy available
- Female participants of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female participants must be 1 year post-menopausal orsurgically sterile, Women of childbearing potential who are sexually active with a non-sterilized male partner must agree to follow their chemotherapy provider's instructions for birth control.
- Participants should have adequate organ function to tolerate chemotherapy, as defined by:
- peripheral granulocyte count of > 1,500/mm3
- platelet count > 100,000/mm3
- hemoglobin >9 g/dL
- total bilirubin < 1.5 x upper limit of normal (ULN)
- aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each < 1.5 x ULN
- serum creatinine < 1.5 x ULN
- INR/PT/PTT each < 1.5 x ULN
- Able to swallow oral formulation of the study agent
- Subjects should not donate blood while participating in this study, or for at least 90 days following the last dose of chemotherapy
Who cannot join
- Participants who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node biopsy and therefore cannot be assessed accurately for pathologic response, are not eligible.
- Participants currently pregnant or breastfeeding.
- Participants for whom any of the planned chemotherapies are contraindicated.
- Participants with currently diagnosed type I or II diabetes mellitus.
- Participants taking any antidiabetic medication that would affect insulin resistance or hyperinsulinemia (i.e. TZD, GLP-1RA, DPP-4i, SGLT2i, metformin) in the past one month.
- Participants with history of hypersensitivity reaction to dapagliflozin.
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- Participants with eGFR < 25.
- History of recurrent (three or more occurrences within 12 months, or two or more occurrences within 6 months) urinary tract infections.
- Currently participating in weight loss programs or weight change in the past 3 months (> 5% current body weight) or have a history of gastrointestinal surgery.
- Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, intranasal influenza, rabies, BCG, and typhoid vaccine.
- Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale Cancer Center Smilow Cancer Hospital
New Haven, Connecticut, 06520
About this study
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
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.
Read the detailed description
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 assess tissue expression of insulin signaling intermediates and SGLT2 by immunohistochemistry (IHC) on pre- and post-treatment tissue samples.
Outcomes will be assessed before treatment and 12 weeks post treatment (after completion of all neoadjuvant therapy but before surgery).
Registration (including outcome measures) was updated to reflect current protocol July 2024.
- Conditions
- Breast Cancer, Hyperinsulinism, HER2-negative Breast Cancer
- Being tested
- Dapagliflozin 10mg
- Medical subject headings
- Breast Neoplasms, Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10mgDrug
10 mg tablets for oral administration daily throughout chemotherapy treatment
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Experimental | 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. Receives: Drug: Dapagliflozin 10mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
Change in HOMA-IR (calculated as fasting insulin (μU/ml) x fasting glucose (mmol/l) divided by 22.5.
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Secondary outcomes (7)
Change in Fasting glucose concentration
Fasting plasma glucose concentration will be assessed following an overnight fast at baseline and 12 weeks post treatment
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Change in Fasting insulin concentration
Fasting plasma insulin concentration will be assessed at baseline and 12 weeks post treatment
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated PKB/AKT
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.
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated insulin receptor
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.
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R)
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.
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated insulin receptor substrate (IRS) 1
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.
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Sodium-glucose cotransporter-2 (SGLT2)
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.
Measured: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start15 Oct 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maryam Lustberg, MD, MPH, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05989347
- Sponsor's protocol ID
- 2000033529
- Other IDs
- No NIH funding
- Status last verified
- May 2026
- First submitted
- 3 Aug 2023
- Last updated
- 22 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05989347
- Acronym / sponsor ID
- 2000033529
- Conditions
- Breast Cancer, Hyperinsulinism, HER2-negative Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 15 Oct 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 14 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 assess tissue expression of insulin signaling intermediates and SGLT2 by immunohistochemistry (IHC) on pre- and post-treatment tissue samples.
Outcomes will be assessed before treatment and 12 weeks post treatment (after completion of all neoadjuvant therapy but before surgery).
Registration (including outcome measures) was updated to reflect current protocol July 2024.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Experimental | Drug: Dapagliflozin 10mgAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Women > 18 years of age with newly diagnosed, histologically confirmed, clinical stage I-III, HER2-negative - either ER+ or triple negative - invasive breast cancer as defined by ASCO CAP guidelines for whom neoadjuvant chemotherapy would be indicated. The following chemotherapy regimens are acceptable:
- BMI ≥ 25 kg/m2
- Hyperinsulinemia defined as HOMA-IR ≥ 2.5.
- Willing and able to provide written informed consent for the trial.
- Has at least one (1) physical 4-5-micron single H\&E slide from diagnostic biopsy available
Key exclusion criteria (11 listed)
- Participants who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node biopsy and therefore cannot be assessed accurately for pathologic response, are not eligible.
- Participants currently pregnant or breastfeeding.
- Participants for whom any of the planned chemotherapies are contraindicated.
- Participants with currently diagnosed type I or II diabetes mellitus.
- Participants taking any antidiabetic medication that would affect insulin resistance or hyperinsulinemia (i.e. TZD, GLP-1RA, DPP-4i, SGLT2i, metformin) in the past one month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 10mg10 mg tablets for oral administration daily throughout chemotherapy treatment | Drug | Dapagliflozin |
Primary outcome
Change in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Change in HOMA-IR (calculated as fasting insulin (μU/ml) x fasting glucose (mmol/l) divided by 22.5.
7 secondary outcomes
Change in Fasting glucose concentration
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Change in Fasting insulin concentration
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated PKB/AKT
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated insulin receptor
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R)
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Total and phosphorylated insulin receptor substrate (IRS) 1
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Sodium-glucose cotransporter-2 (SGLT2)
Time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Maryam Lustberg, MD, MPH principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dapagliflozin 10mg in people with Breast Cancer and Hyperinsulinism, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carl Brown (475-241-1065, carl.brown@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) (time frame: baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.