RECRUITING

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

Conditions

Breast Cancer Hyperinsulinism HER2-negative Breast Cancer

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2024-10-15

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05989347

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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.

Inclusion Criteria

Exclusion 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

* 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.

Contacts and Locations

Study Contact

Adam Blanchard, MS

CONTACT

(203) 499-9297

adam.blanchard@yale.edu

Principal Investigator

Maryam Lustberg, MD, MPH

PRINCIPAL_INVESTIGATOR

Yale University

Study Locations (Sites)

Yale Cancer Center Smilow Cancer Hospital

New Haven, Connecticut, 06520

United States

Collaborators and Investigators

Sponsor: Yale University

Maryam Lustberg, MD, MPH, PRINCIPAL_INVESTIGATOR, Yale University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-15

Study Completion Date2025-12

Study Record Updates

Study Start Date2024-10-15

Study Completion Date2025-12

Terms related to this study

Additional Relevant MeSH Terms

Breast Cancer
Hyperinsulinism
HER2-negative Breast Cancer