Breast Cancer Clinical Trial
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
Summary
This is a Phase II, multicenter, randomized, open-label, active-controlled trial 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 HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation following progression on or after endocrine-based therapy.
Full Description
The study will only include participants who have at least one baseline risk factor for the development of severe hyperglycemia, defined as:
Diabetes (FPG ≥ 126 mg/dL or ≥ 7.0 mmol/L and/or HbA1c ≥ 6.5%)
Pre-diabetes (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 (BMI ≥ 30)
Age ≥ 75 years Participants will be randomized in a 1:1 ratio (approximately 66 participants in each treatment arm) to receive the combination of dapagliflozin plus metformin XR or metformin XR alone starting on Cycle 1 Day 1. For both arms participants will receive fulvestrant starting at Cycle 1 Day 1 and alpelisib starting at Cycle 1 Day 8. Randomization will be stratified by diabetic status at baseline, i.e. normal vs pre- diabetic/diabetic (based on fasting plasma glucose (FPG) and/or hemoglobin A1c (HbA1c) laboratory values).
The study will consist of a 28-day screening phase, a 12 cycle treatment phase, and a post-treatment phase which includes safety and efficacy follow-up (if applicable).
Eligibility Criteria
Inclusion Criteria:
Participant has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer by local laboratory
Participant has a PIK3CA mutation(s) present in tumor prior to enrollment
Participant has prior treatment with an endocrine-based treatment (i.e. letrozole, anastrozole, exemestane, fulvestrant or oral SERD) and may be:
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
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
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 will NOT be included in the study.
Participants may or may 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, then the participant is postmenopausal
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Participant has adequate bone marrow and organ function
Exclusion Criteria:
Participant who 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 has received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), any PI3K, Mammalian Target of Rapamycin (mTOR) or Protein Kinase B (Akt) inhibitor
Participant has 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 has a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis
Participant has currently documented pneumonitis/interstitial lung disease
Participant has 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)
Other inclusion/exclusion criteria may apply
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 2 Locations for this study
Saint Louis Missouri, 63110, United States
Hong Kong , , Hong Kong
Kuala Lumpur , 59100, Malaysia
How clear is this clinincal trial information?