A phase III randomized, double blind, placebo controlled study of BKM120 with fulvestrant, in postmenopausal women with hormone receptor-positive HER2-negative AI treated, locally advanced or metastatic breast cancer who progressed on or after mTOR inhibitor based treatment-(BKM 120-2303)


This study is a multicenter, randomized, double-blind placebo controlled phase iii trial.

Patient will be randomized in a 2:1 ratio to one of the two treatment arms:
* BKM120 100 mg plus fulvestrant 500 mg
* Placebo plus fulvestrant 500 mg

During treatment phase, BKM120 100 mg or placebo will be administered orally once daily starting on cycle 1 day 1 on a continuous dosing schedule in combination with fulvestrant 500 mg starting on cycle 1 day 1, cycle 1 day 15 and day 1 of every cycle thereafter in a 28 day cycle. Treatment crossover from placebo to BKM120 will not be permitted in this study.

a complete cycle of treatment is defined as 28 days ((+-) 3 days) of once daily treatment of BKM120 or placebo in combination with fulvestrant.

The study drug and placebo (BKM120/placebo) will be administered as an oral gelatine capsule at 100 mg (2x 50 mg capsules1) once daily starting from cycle 1 day 1

The other study drug , fulvestrant will be adminsitered by injection for i.m. with an administration of 500 mg at days 1, 15 on cycle 1 and day 1 at each cycle thereafter

Participant Eligibility

* Patient has radiologic evidence of inoperable locally advanced or metastatic breast cancer

* Patient has archival tumor tissue for the analysis of PI3K-related biomarkers

* Patient has a PI3K pathway activation status defined by a Novartis designated laboratory as activated, non-activated or unknown before randomization provided sufficient amount of tumor tissues was present in the patient[Single Quote]s archival sample

* Patient has HER2- and estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory testing.

* Patient is postmenopausal. Postmenopausal status is defined either by

* Prior bilateral oophorectomy

* Age >=60

* Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression), and FSH and estradiol in the postmenopausal range (serum FSH > 40 mIU/mL and estradiol <20 pg/mL or according to the postmenopausal range definition for the laboratory involved).
For women with therapy-induced amenorrhea, oophorectomy or serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status.

Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LHRH)
agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression.

* Patient must have received prior treatment with AIs either in the neo/adjuvant or locally advanced/metastatic setting. Patients can receive any number of endocrine/hormonal lines of therapy before study entry

* Patient has radiological or objective evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry. Progression must have occurred while on, or within 30 days of the end of treatment of the regimen. Patients who had to withdraw one of the two agents due to safety reasons will still be eligible at the time of disease progression on the single-agent (either endocrine therapy or mTORi).

* Patient must have as per RECIST 1.1 measurable disease or nonmeasurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease

* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status <= 2 which the investigator believes is stable at the time of screening