Evaluating Dapagliflozin with Neoadjuvant Therapy for HER2-negative Breast Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial aims to assess the safety and effectiveness of dapagliflozin, a medication used to manage blood sugar levels, in women with early-stage HER2-negative breast cancer undergoing neoadjuvant therapy. The study will measure changes in metabolic plasma markers of insulin resistance, specifically fasting glucose and insulin levels, in participants receiving this treatment. It is an open-label, single-arm trial that will also evaluate the safety of combining dapagliflozin with standard chemotherapy regimens. The goal is to determine if dapagliflozin can improve insulin signaling and overall treatment outcomes for these patients.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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:

  1. Weekly or dose dense paclitaxel, followed by dose dense doxorubicin plus cyclophosphamide
  2. Docetaxel plus cyclophosphamide
  3. Docetaxel plus carboplatin plus or minus pembrolizumab
  4. 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
* 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:

  1. peripheral granulocyte count of \> 1,500/mm3
  2. platelet count \> 100,000/mm3
  3. hemoglobin \>9 g/dL
  4. total bilirubin \< 1.5 x upper limit of normal (ULN)
  5. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each \< 1.5 x ULN
  6. serum creatinine \< 1.5 x ULN
  7. 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

Exclusion Criteria:

* 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.
* 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.

Where it's running

• Yale Cancer Center Smilow Cancer Hospital
  New Haven, Connecticut, United States Recruiting

Study contacts

• Principal investigator: Maryam Lustberg, MD, MPH — Yale University
• Study coordinator: Carl Brown
• Email: carl.brown@yale.edu
• Phone: 475-241-1065

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.