Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fulvestrant; Alpelisib; Alpelisib placebo
Intervention MeSH terms: Fulvestrant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 572.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BYL719; HR+; HER2-negative; advanced breast cancer; alpelisib; fulvestrant; PI3K; Phase III; ER+; PgR+; men; postmenopausal; aromatase inhibitor; neoplasms

Summary:

      To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free
      survival compared to fulvestrant and placebo in men and postmenopausal women with hormone
      receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment
      with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  If female, patient is postmenopausal

          -  Patient has identified PIK3CA status

          -  Patients may be:

               -  relapsed with documented evidence of progression while on (neo) adjuvant
                  endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine
                  therapy with no treatment for metastatic disease;

               -  relapsed with documented evidence of progression more than 12 months from
                  completion of (neo)adjuvant endocrine therapy and then subsequently; progressed
                  with documented evidence of progression while on or after only one line of
                  endocrine 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 therapy

          -  Patient has recurrence or progression of disease during or after AI therapy (i.e.

        letrozole, anastrozole, exemestane).

          -  Patient has a histologically and/or cytologically confirmed diagnosis of
             estrogen-receptor positive breast cancer by local laboratory and has HER2 negative
             breast cancer

          -  Patient has either measurable disease per RECIST 1.1 criteria OR at least one
             predominantly lytic bone lesion must be present

          -  Patient has adequate bone marrow function

        Exclusion Criteria:

          -  Patient with symptomatic visceral disease or any disease burden that makes the patient
             ineligible for endocrine therapy per the investigator's best judgment

          -  Patient has received prior treatment with chemotherapy (except for neoadjuvant/
             adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor (pre-treatment
             with CDK4/6 inhibitors is allowed)

          -  Patient with inflammatory breast cancer at screening

          -  Patients with Child pugh score B or C

          -  Patients with an established diagnosis of diabetes mellitus type I or not controlled
             type II

          -  Patient has Eastern Cooperative Oncology Group (ECOG) performance status 2 or more

          -  Patient with CNS involvement unless he/she is at least 4 weeks from prior therapy
             completion to starting the study treatment and has stable CNS tumor at time of
             screening and not receiving steroids and/or enzyme inducing ant-epileptic medications
             for brain metastases

          -  Patient has participated in a prior investigational study within 30 days prior to
             enrollment or within 5 half-lives of the investigational product, whichever is longer

          -  Patient has a history of acute pancreatitis within 1 year of screening or a past
             medical history of chronic pancreatitis

          -  Patient who relapsed with documented evidence of progression more than 12 months from
             completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease

        Other protocol-defined inclusion/esclusion criteria may apply.