Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant with Neoadjuvant Therapy

Launched by YALE UNIVERSITY · Aug 3, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the safety and effects of a medication called dapagliflozin for women with early-stage HER2-negative breast cancer who are about to start chemotherapy. The main goal is to look at certain markers in the blood that indicate how the body processes insulin, which is important for understanding how the drug might help in managing their condition during treatment.

To be eligible for this trial, women need to be over 18 years old and have a specific type of breast cancer that has been diagnosed through a biopsy. They should also have a body mass index (BMI) of 25 or higher and experience high levels of insulin in their blood. Participants will need to be able to take the medication by mouth and have good overall health to handle chemotherapy. During the trial, they will receive dapagliflozin along with standard chemotherapy treatment and will be monitored closely for any side effects and changes in their health. It’s important to note that women who are pregnant, breastfeeding, or have certain health conditions may not be able to participate.

Gender

FEMALE

Eligibility criteria

• 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.