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
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Alpelisib; Fulvestrant; Metformin XR; Dapagliflozin + metformin XR; Dapagliflozin
Intervention description: Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 8 in a 28 days cycle.; 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.; 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.; 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; 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
Intervention MeSH terms: Metformin; Dapagliflozin; Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Alpelisib; Fulvestrant; Metformin XR; Dapagliflozin + metformin XR; Advanced breast cancer; Phase II; HR+; HER2-; PIK3CA; Hyperglycemia

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.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Participant had a histologically and/or cytologically confirmed diagnosis of estrogen
             receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer by
             a local laboratory.

          -  Participant had a PIK3CA mutation(s) present in the tumor prior to enrollment.

          -  Participant had prior treatment with an endocrine-based treatment (e.g. letrozole,
             anastrozole, exemestane, fulvestrant, or oral SERD) and may have fallen into one of
             the following categories:

               1. Relapsed with documented evidence of progression while on (neo) adjuvant
                  endocrine-based therapy or within 12 months from completion of (neo) adjuvant
                  endocrine-based therapy with no treatment for metastatic disease.

               2. Relapsed with documented evidence of progression more than 12 months from
                  completion of (neo) adjuvant endocrine-based therapy and then subsequently
                  progressed with documented evidence of progression while on or after only one
                  line of endocrine-based therapy for metastatic disease.

               3. Newly diagnosed advanced breast cancer, then relapsed with documented evidence of
                  progression while on or after only one line of endocrine-based therapy.

        Note: Participants with newly diagnosed endocrine-based treatment naïve advanced breast
        cancer were NOT included in the study.

          -  Participants might or might not have received prior CDK4/6i therapy. If prior CDK4/6i
             therapy was administered, it may have been in the adjuvant or metastatic setting.

          -  If female, the participant was postmenopausal.

          -  Participant had an Eastern Cooperative Oncology Group (ECOG) performance status of 0
             or 1.

          -  Participant had adequate bone marrow and organ function.

        Key Exclusion Criteria:

          -  Participant relapsed with documented evidence of progression more than 12 months from
             completion of (neo) adjuvant endocrine therapy with no treatment for metastatic
             disease.

          -  Participant had more than 1 line of prior treatment in the metastatic setting.

          -  Participant had received prior treatment with chemotherapy (except for
             neoadjuvant/adjuvant chemotherapy), any PI3K, Mammalian Target of Rapamycin (mTOR) or
             Protein Kinase B (Akt) inhibitor.

          -  Participant had inflammatory breast cancer at screening.

          -  Participants with an established diagnosis of diabetes mellitus type I or participants
             with type II diabetes mellitus requiring antihyperglycemic therapy.

          -  Participant had a history of acute pancreatitis within 1 year of screening or a past
             medical history of chronic pancreatitis.

          -  Participant had currently documented pneumonitis/interstitial lung disease.

          -  Participant had a history of severe cutaneous reaction, such as Steven-Johnson
             Syndrome (SJS), erythema multiforme (EM), Toxic Epidermal Necrolysis (TEN) or Drug
             Reaction with Eosinophilia and Systemic Syndrome (DRESS).