Dapagliflozin for Early-Stage Breast Cancer

Overseen By Carl Brown

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Antidiabetics, SGLT2i, Metformin, others

Disqualifiers: Diabetes, Pregnancy, Breastfeeding, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how dapagliflozin, a medication, might help with insulin resistance in individuals with early-stage HER2-negative breast cancer undergoing chemotherapy. The focus is on how this medicine affects specific blood markers related to insulin resistance. It targets women with this type of breast cancer who are overweight (BMI of 25 or more) and have high insulin levels but do not have diabetes. Participants should be prepared to take daily oral medication alongside their standard chemotherapy treatment. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that participants stop taking any antidiabetic medications that affect insulin resistance or hyperinsulinemia, such as TZD, GLP-1RA, DPP-4i, SGLT2i, and metformin, at least one month before joining the study.

Is there any evidence suggesting that dapagliflozin is likely to be safe for humans?

Research has shown that dapagliflozin, a drug commonly used for diabetes, is generally well-tolerated. In studies supporting heart health during cancer treatment, dapagliflozin showed no major safety issues. The FDA has already approved dapagliflozin for diabetes, indicating its relative safety. However, as this trial is in its early stages, further research is necessary to confirm its safety for individuals with early-stage breast cancer. The trial will closely monitor participants for any side effects to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for early-stage breast cancer, which typically involve chemotherapy, surgery, and radiation, dapagliflozin offers a novel approach by targeting insulin resistance. Dapagliflozin, commonly used as a diabetes medication, works by inhibiting a protein that helps reabsorb glucose in the kidneys, thereby lowering blood sugar levels. Researchers are excited about dapagliflozin because it may enhance the effectiveness of chemotherapy by altering the metabolic environment of cancer cells, potentially making them more responsive to treatment. This unique mechanism could provide an additional benefit for patients with insulin resistance and specific breast cancer types.

What evidence suggests that dapagliflozin might be an effective treatment for early-stage breast cancer?

Research has shown that dapagliflozin, a drug commonly used for diabetes, might help treat breast cancer. In this trial, all participants will receive dapagliflozin alongside their standard neoadjuvant chemotherapy. Studies suggest that this medication can cause cancer cells to die, potentially leading to smaller tumors. This is particularly important for early-stage HER2-negative breast cancer, the focus of this study. Although direct evidence in humans is limited, the drug's ability to lower insulin resistance might benefit patients, as insulin resistance is linked to cancer growth. Overall, these findings suggest dapagliflozin could be a promising addition to current breast cancer treatments. ^{2 4 6 7 8}

Who Is on the Research Team?

Maryam Lustberg, MD, MPH

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for women with early-stage HER2-negative breast cancer, BMI ≥ 25 kg/m², and hyperinsulinemia (HOMA-IR ≥ 2.5). They must be willing to use two birth control methods or abstain from sex, have no history of severe allergies to dapagliflozin, not currently pregnant/breastfeeding, without diabetes mellitus or recent significant weight changes.

Inclusion Criteria

I am a woman who can have children and have a recent negative pregnancy test.

I am willing to have a biopsy after 12 weeks of treatment.

I will not donate blood during the study or for 3 months after my last chemotherapy dose.

Exclusion Criteria

I have been diagnosed with type I or II diabetes.

I have not received any live vaccines in the last 30 days.

I have not had certain breast surgeries that make it hard to assess my cancer response.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin concomitant with neoadjuvant therapy, including chemotherapy regimens such as weekly paclitaxel and ddAC

12 weeks

Weekly visits for paclitaxel treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of metabolic plasma markers and tissue expression

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The study tests the effects of Dapagliflozin (10mg) on insulin resistance markers in patients undergoing neoadjuvant therapy for breast cancer. It involves taking Dapagliflozin alongside standard chemotherapy regimens and assessing metabolic changes.

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12400668/

SGLT2i Dapagliflozin in primary prevention of ... The PROTECT trial is the first randomized clinical study designed to evaluate whether Dapagliflozin can reduce anthracycline- and/or trastuzumab ...

2. yalemedicine.org yalemedicine.org/clinical-trials/pilot-study-to-evaluate-biomarkers-and-safety-of-dapagliflozin-concomitant-with-neoadjuvant-therapy

A pilot study to evaluate biomarkers and safety of ... The primary objective of the study is to assess metabolic plasma markers of insulin resistance in patients with early-stage HER2-negative breast ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10813754/

Antidiabetic Drugs in Breast Cancer Patients - PMC This review explores the link between diabetes and an elevated risk of breast cancer, highlighting the global prevalence of these conditions.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299924004916

Exploring the anti-cancer potential of SGLT2 inhibitors in ... SGLT2 inhibitors have been found to induce apoptosis in breast cancer cells, potentially contributing to tumor reduction.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05025735

NCT05025735 | Alpelisib, Fulvestrant and Dapagliflozin for ... Alpelisib is a p110α specific PI3K inhibitor that has shown significant clinical benefit in patients with HR+/HER2 negative mBC harboring activating PIK3CA ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05989347

NCT05989347 | Study to Evaluate Biomarkers and Safety ... The primary objective of the study is to assess metabolic plasma markers of insulin resistance in patients with early-stage HER2-negative breast cancers ...

7. medicine.yale.edu medicine.yale.edu/trial/pilot-study-to-evaluate-biomarkers-and-safety-of-dapagliflozin-concomitant-with-neoadjuvant-therapy/

A pilot study to evaluate biomarkers and safety of dapagliflozin ... The primary objective of the study is to assess metabolic plasma markers of insulin resistance in patients with early-stage HER2-negative breast ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06341842?cond%3Dcancer%26intr%3DSGLT2%20inhibitor%26viewType%3DTable%26rank%3D8

Study Details | NCT06341842 | Potential Protective Role of ... The purpose of this study is to evaluate whether dapagliflozin reduces chemotherapy-induced cardiotoxicity in participants with breast cancer treated with ...