Conditions: Metastatic Breast Cancer HER2+ Breast Cancer
Keywords: HER2 BKM120 PIK3 metastatic breast cancer brain metastases Herceptin trastuzumab capecitabine open-label maximum tolerated dose Phase I/Phase ll
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 72
Healthy volunteers: no

Brief summary:
This study will assess the safety and efficacy of BKM120 in combination with trastuzumab in patients with relapsing HER2 overexpressing breast cancer who have previously failed trastuzumab.

The study will further assess the safety and preliminary efficacy of BKM120 in combination with trastuzumab and capecitabine in patients with relapsing HER2 overexpressing breast cancer and brain metastases (BM) who have previously failed trastuzumab.

Detailed description:

Arms:
arm 1: Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab arm 2: Patients with HER2-overexpressing metastatic breast cancer and brain metastases, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab

Interventions: intervention 1: BKM120 intervention 2: Trastuzumab intervention 3: Capecitabine
Intervention descriptions: intervention 1: Buparlisib (BKM120) is the investigational drug. Burparlisib was supplied as 10 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area. Buparlisib capsules were packaged in high density polyethylene bottles with a plastic child resistant closure. intervention 2: Trastuzumab was used in this study according to the local regulations in each participating country. A loading dose (4 mg/kg) of trastuzumab was administered (if required as assessed by the principal Investigator based on the timing of the last trastuzumab dose prior to enrollment) on Day -7 over 90 minutes, followed by weekly intravenous infusion of 2 mg/kg maintenance doses from Day 1 of Cycle 1 (over 30 minutes if the previous infusion was well tolerated). intervention 3: 1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.

Protocol document: