Health Condition 1: - Health Condition 2: R978- Other abnormal tumor markers
Conditions
Interventions
Intervention1: Alpelisib plus Fulvestrant plus Dapagliflozin plus Metformin XR: Alpelisib 300mg orally once daily starting at Cycle 1 Day 8 in combination with fulvestrant 500mg intramuscular at Cycle
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1 Participant has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive (ER plus) and/or progesterone receptor positive (PgR plus) breast cancer by local laboratory 2 Participant has a PIK3CA mutation(s) present in tumor prior to enrollment 3 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 endocrinebased 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. 4 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 5 If female, then the participant is postmenopausal 6 Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 7 Participant has adequate bone marrow and organ function
Exclusion criteria
Exclusion criteria: 1 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 2 Participant had more than 1 line of prior treatment in the metastatic setting 3 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 4 Participant has inflammatory breast cancer at screening 5 Participant with an established diagnosis of diabetes mellitus type I or participants with type II diabetes mellitus requiring antihyperglycemic therapy 6 Participant has a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis 7 Participant has currently documented pneumonitis/interstitial lung disease 8 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the reduction in severe hyperglycemia events over the first eight weeks of alpelisib plus fulvestrant with prophylactic dapagliflozin plus metformin XR compared to alpelisib plus fulvestrant with prophylactic metformin XRTimepoint: Occurrence of severe hyperglycemia (grade â?¥ 3, based on glucose laboratory values) over the first eight weeks of alpelisib plus fulvestrant treatment (from C1D8 to C3D8) | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerabilityTimepoint: Safety: Incidence, type, and severity of adverse events per CTCAE version 4.03 criteria including changes in laboratory values, ECOG, vital signs, liver assessments, renal and cardiac assessments Tolerability: dose interruptions, reductions, dose intensity, and duration of exposure for all drug components;To evaluate alpelisib plus fulvestrant with prophylactic dapagliflozin plus metformin XR compared to alpelisib plus fulvestrant with prophylactic metformin XR with regard to preliminary efficacy parametersTimepoint: PFS, ORR with confirmed response and CBR with confirmed response, based on local radiology assessments and using RECIST 1.1 criteria | — |
Countries
Argentina, Hong Kong, India, Malaysia, Philippines, Russian Federation, Saudi Arabia, Singapore, United States of America
Contacts
Public ContactMurugananthan K
Novartis Healthcare PVT LTD
Outcome results
None listed