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

NCT05989347 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2000033529No NIH funding
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer; Hyperinsulinism; HER2-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy

Secondary Outcomes (7)

• Change in Fasting glucose concentration

  baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy

• Change in Fasting insulin concentration

  baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy

• Total and phosphorylated PKB/AKT

  baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy

• Total and phosphorylated insulin receptor

  baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy

• Total and phosphorylated insulin-like growth factor-1 receptor (IGF1R)

  baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy

Study Arms (1)

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.

Drug: Dapagliflozin 10mg

Interventions

Dapagliflozin 10mg DRUG

10 mg tablets for oral administration daily throughout chemotherapy treatment

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale Cancer Center Smilow Cancer Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Hyperinsulinism

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Maryam Lustberg, MD, MPH

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carl Brown

CONTACT

475-241-1065; carl.brown@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 14, 2023
• Study Start: October 15, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)