Dapagliflozin for Early-Stage Breast Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Maryam Lustberg, MD, MPH

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Yale University

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

Disqualifiers: Diabetes, Pregnancy, Breastfeeding, others

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

How does the drug dapagliflozin differ from other treatments for early-stage breast cancer?

Dapagliflozin is unique because it is originally a diabetes medication that works by helping the kidneys remove sugar from the body through urine. Its use in early-stage breast cancer is novel, as it is not a standard cancer treatment and its effects on cancer are still being studied.

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Eligibility Criteria

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 not received any live vaccines in the last 30 days.

I have been diagnosed with type I or II diabetes.

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

Trial Timeline

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)

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Yale Cancer Center Smilow Cancer Hospital New Haven, CT

Who Is Running the Clinical Trial?

Yale University Lead Sponsor

AstraZeneca Industry Sponsor

References

1. Belgium pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. [2021] Dapagliflozin, a specific inhibitor of sodium-glu¬cose cotransporters type 2 (SGLT2, inhibits glucose reabsorp¬tion in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c), with a minor risk of hypoglycaemia, a weight reduction and a reduction in arterial blood pressure. The efficacy of empagliflozin on HbA1c reduction increases according to the level of hyper¬glycaemia but decreases in patients with renal insufficiency. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. Dapagliflozin (Forxiga®), 10 mg once daily, is indicated for the treatment of T2DM and reim¬bursed in Belgium with conditions as add-on to a background glucose-lowering therapy (either metformin or sulfonylurea/ repaglinide or metformin plus sulfonylurea/repaglinide or basal insulin plus at least one of these oral glucose-lowering agents). Preliminary results suggest some cardiovascular and renal protection. These results should be confirmed in an ongoing large prospective controlled trial (DECLARE) in type 2 diabetic patients at high cardiovascular risk.

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021] Dapagliflozin (DAPA) (Farxiga or Forxiga) is a sodium glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes mellitus(T2DM) treatment.

3. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. [2022] Dapagliflozin (Forxiga(®), Farxiga(®)) is an orally administered sodium-glucose co-transporter-2 (SGLT2) inhibitor used in the management of patients with type 2 diabetes. Dapagliflozin reduces renal glucose reabsorption by inhibiting the transporter protein SGLT2 in the renal proximal tubule, thereby increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of insulin secretion or action; therefore, dapagliflozin provides complementary therapy when used in combination with other antihyperglycaemic drugs. This article updates an earlier review of dapagliflozin and focuses on longer-term efficacy and tolerability data (e.g. from extensions of earlier clinical trials), as well as data from studies in special patient populations (e.g. history of cardiovascular disease). Numerous well-designed clinical trials with dapagliflozin, primarily as add-on therapy for 24 weeks (but also as monotherapy or initial combination therapy), have consistently demonstrated reductions in glycosylated haemoglobin, fasting plasma glucose levels and bodyweight. Extensions of these trials show the effects are maintained over longer-term follow-up periods of ≈1-4 years and dapagliflozin is generally well tolerated. Dapagliflozin has a low risk of hypoglycaemia, although the incidence varies depending on background therapy, and genital mycotic infections (particularly in women) are the most common adverse events. Dapagliflozin is not recommended in patients with moderate or severe renal impairment. In view of its unique mechanism of action and now well-established efficacy and tolerability profile, dapagliflozin is a useful treatment option in the management of type 2 diabetes, although its effects on diabetic complications remain to be evaluated.

4. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021] To review clinical evidence for the efficacy, safety, and tolerability of dapagliflozin (Farxiga-AstraZeneca), a sodium glucose cotransporter 2 inhibitor, as monotherapy or in combination with other hypoglycemic agents for the treatment of type 2 diabetes.

5. United States pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023] Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.