NCT04899349

Study of Safety and Efficacy of Dapagliflozin + Metformin XR Versus Metformin XR in Participants With HR+, HER2-, Advanced Breast Cancer While on Treatment With Alpelisib and Fulvestrant

EPIK-B4: A Phase II, Multicenter, Randomized, Open-label, Active-controlled Study to Assess the Safety and Efficacy of Dapagliflozin + Metformin XR Versus Metformin XR During Treatment With Alpelisib (BYL719) in Combination With Fulvestrant in Participants With HR+, HER2-, Advanced Breast Cancer With a PIK3CA Mutation Following Progression on/After Endocrine-based Therapy

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study was designed to assess the safety and efficacy of the combination of dapagliflozin plus metformin extended release (XR) compared with metformin XR during treatment with alpelisib plus fulvestrant in participants with Hormone Receptor (HR)-positive, Human Epidermal growth factor Receptor-2 (HER2)-negative advanced breast cancer with a Phosphoinositide-3-Kinase Catalytic subunit Alpha (PIK3CA) mutation following progression on or after endocrine-based therapy.

Detailed description

This was a multicenter, randomized, open-label, active-controlled trial, stratified by diabetic status at baseline (i.e., normal vs prediabetic/diabetic based on fasting plasma glucose (FPG) and/or Hemoglobin A1c (HbA1c) laboratory values). The study included only participants with at least one baseline risk factor for the development of severe hyperglycemia which were diabetes (FPG ≥ 126 milligram (mg)/deciliter (dL) or ≥ 7.0 millimole (mmol)/liter (L) and/or HbA1c ≥ 6.5%), prediabetes (FPG ≥ 100 mg/dL to \< 126 mg/dL or 5.6 to \< 7.0 mmol/L and/or HbA1c 5.7 to \< 6.5%), obesity (body mass index \[BMI\] ≥ 30) and age (≥ 75 years). The planned duration of treatment with alpelisib and fulvestrant was 12 cycles (28 days in each cycle) or until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason, whichever came first. Approximately 66 participants in each treatment arm were planned to be randomized to receive the combination of alpelisib and fulvestrant with either dapagliflozin plus metformin extended release (XR) or metformin XR alone. As a result of the early termination of the study due to emerging data demonstrating the impact of prophylactic metformin and slow recruitment, only 2 participants were enrolled in the study.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Alpelisib	Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 8 in a 28 days cycle.
DRUG	Fulvestrant	Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 after randomization and then at Day 1 of each subsequent cycle during the randomized treatment phase.
DRUG	Metformin XR	Metformin XR (tablets) administered at a starting dose of 500mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 days cycle. Dose titration from 500 mg once a day to 2000 mg once a day.
DRUG	Dapagliflozin + metformin XR	Dapagliflozin + metformin XR administered as a single tablet combination at a starting dose of 5 mg dapagliflozin + 500 mg metformin XR orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 days cycle. Dose titration from 5 mg dapagliflozin + 500 mg metformin XR orally once daily to 10 mg dapagliflozin + 2000 mg metformin XR once daily
DRUG	Dapagliflozin	Dapagliflozin (tablet) at a starting dose of 5mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 days cycle. Dose titration from 5 mg to 10 mg once daily

Timeline

• Start date: 2022-04-06
• Primary completion: 2023-05-10
• Completion: 2023-05-10
• First posted: 2021-05-24
• Last updated: 2024-10-09
• Results posted: 2023-12-12

Locations

2 sites across 2 countries: United States, Malaysia

Regulatory

• FDA-regulated drug study