RecruitingPhase 1NCT05989347

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

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

Sponsor

Yale University

Enrollment

20 participants

Start Date

Oct 15, 2024

Study Type

INTERVENTIONAL

Conditions

Breast Cancer HER2-negative Breast Cancer Hyperinsulinism

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.

Eligibility

Sex: FEMALEMin Age: 18 Years

Inclusion Criteria21

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
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

Exclusion Criteria11

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.