NCT05989347

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a single arm, open label trial that will evaluate changes in plasma markers of insulin resistance, namely, fasting glucose and insulin, measured as the HOMA-IR score, as well as the safety of the addition of dapagliflozin to neoadjuvant treatment in hyperinsulinemic women with newly diagnosed early stage HER2-negative breast cancers who are candidates for neoadjuvant therapy. Hypotheses are: (i) the SGLT2 inhibitor, dapagliflozin, administered concomitantly with weekly neoadjuvant therapy in hyperinsulinemic women with newly diagnosed HER2-negative breast cancers will lead to a decrease in fasting plasma insulin and glucose and thus, a downregulation in downstream insulin signaling in the tumor as measured by Protein kinase B (PKB)/AKT phosphorylation. (ii) that dapagliflozin can be safely coadministered at full dose with multiagent chemotherapy or chemo-immunotherapy. Routine, standard of care neoadjuvant chemotherapy, with or without immunotherapy, will be given together with the investigational product. Acceptable chemotherapy regimens include: 1) weekly paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments (ddAC-T; ); 2) pembrolizumab every 3 weeks (Q3W), with carboplatin + weekly paclitaxel (cycles 1-4) x12 weeks followed by ddAC x 4 treatments (cycles 5-8) (KEYNOTE-522 regimen; only for participants with stage II-III ER/PR and HER-negative breast cancer); 3) docetaxel plus cyclophosphamide and 4) docetaxel plus carboplatin. The primary objective of the study is to assess metabolic plasma markers of insulin resistance in participants with early-stage HER2-negative breast cancers receiving dapagliflozin concomitant with neoadjuvant therapy. Secondary objectives are to assess tissue expression of insulin signaling intermediates and SGLT2 by immunohistochemistry (IHC) on pre- and post-treatment tissue samples. Outcomes will be assessed before treatment and 12 weeks post treatment (after completion of all neoadjuvant therapy but before surgery). Registration (including outcome measures) was updated to reflect current protocol July 2024.

Conditions

• Breast Cancer
• Hyperinsulinism
• HER2-negative Breast Cancer

Interventions

Type	Name	Description
DRUG	Dapagliflozin 10mg	10 mg tablets for oral administration daily throughout chemotherapy treatment

Timeline

• Start date: 2024-10-15
• Primary completion: 2025-12-01
• Completion: 2025-12-01
• First posted: 2023-08-14
• Last updated: 2025-03-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study