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)

Study ID
STU 082012-084

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Todd Morgan
214-648-7020
todd.morgan@utsouthwestern.edu

Principal Investigator
Barbara Haley

Summary

This is a multi-center, randomized, double-blind, placebo controlled phase iii study to determine the efficacy and safety of treatment with BKM120 plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with
HR+ HeR2- ai treated locally advanced or MBC whose disease has progressed on or after mToRi based treatment.

Patients will undergo screening phase and once eligibility (screening criteria met) has been confirmed, the patient will be randomized to one of the two treatment arms in a 2:1 ratio: BKM120 plus fulvestrant arm or placebo
plus fulvestrant arm. Randomization will be stratified according to visceral disease status. Patients will receive treatment until disease progression (assessed by ReCiST 1.1), unacceptable toxicity, death or discontinuation from treatment for any other reasons. Tumor assessments will be performed every 6 weeks after the randomization date until radiological progression (after the final PFS analysis results have been reviewed, the frequency may be reduced to every 12 weeks for patients who have at least 4 post-baseline tumor assessments). after discontinuing the study treatment, the patient will be followed for 30-day safety follow-up, efficacy follow-up (if applicable) and survival follow-up. all patients will be followed for survival status every 3 months regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up).

Patients will be randomized in a 2:1 ratio to receive either: * BKM120 plus fulvestrant -or * Placebo plus fulvestrant

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. There is no specific recommendation regarding the sequence of administration of BKM120/placebo and fulvestrant. a complete cycle of treatment is defined as 28 days ((+-) 3 days) of once daily treatment of BKM120 or placebo in combination with fulvestrant.

BKM120/placebo and fulvestrant dose and treatment schedule: 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 administered by injection for i.m. administration of 500 mg at days 1, 15 on cycle 1, and day 1 at each cycle thereafter.

BKM120/placebo dosing: BKM120 at a dose of 100 mg or placebo will be administered orally once daily on a
continuous dosing schedule starting on cycle 1 day 1 in combination with fulvestrant 500 mg. BKM120/ placebo is dosed on a flat scale of mg/day and not by weight or body surface area. BKM120/placebo will be supplied in 10 mg and 50 mg capsules. There will be no breaks between dosing cycles.

Participant Eligibility


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

* Patient has adequate tumor tissue either archival or new tumor biopsy for the analysis of PI3K-related biomarkers

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

* 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