NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer
NeoPHOEBE will evaluate the efficacy (as defined by pCR) of BKM120 (an oral PI3K inhibitor)
in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled,
neo-adjuvant study in women diagnosed with primary breast cancer >2cm with centrally
confirmed HER2 overexpression or amplification, and who have not previously undergone
treatment for invasive breast cancer.
Prior to the initiation of paclitaxel, there will be a 6-week "biologic window" with
trastuzumab plus BKM120 or placebo only. The study will be conducted separately in two
cohorts (PIK3CA mutated and PI3K3CA wild-type) using a two-stage approach. Within each
cohort patients will be randomized into one of the following treatment arms:
Arm 1: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus
trastuzumab plus weekly paclitaxel for an additional 12 weeks.
Arm 2: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly
paclitaxel for an additional 12 weeks.
After completion of study treatment, patients will undergo definitive surgery.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Pathological complete response (pCR) rate
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) at the time of surgery.
Australia: Department of Health and Ageing Therapeutic Goods Administration