BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer
- Registration Number
- NCT01288092
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This is a prospective, multi-center, open-label, single arm, phase II study with a 2-stage design and Bayesian interim monitoring to investigate the safety and efficacy of BEZ235 in patients with progressive metastatic HR+ HER2- breast cancer who have received at least one prior line of endocrine therapy and two to three prior lines of chemotherapy for metastatic disease. Patients will be stratified into 3 groups according to their PI3K (phosphatidylinositol 3-Kinase) pathway activation status.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Female ≥ 18 years
- ECOG performance status ≤ 2
- Histologically and/or cytologically confirmed diagnosis of breast cancer presenting with metastatic disease (hormone receptor positive and HER2 negative)
- Known PI3K activation status (defined by PIK3CA (Phosphoinositide-3-kinase, catalytic, alpha polypeptide) mutation and PTEN PTEN (Phosphatase and Tensin Homolog) mutation/expression)
- Prior treatment with at least one prior line of endocrine therapy and at least two and no more than three prior lines of chemotherapy for metastatic breast cancer
- Objective and radiologically confirmed progression of disease after prior treatment and at least one measurable lesion as per RECIST
- Adequate bone marrow and organ function
Exclusion Criteria
- Previous treatment with PI3K and/or mTOR inhibitors
- Symptomatic Central Nervous System (CNS) metastases
- Concurrent malignancy or malignancy in the last 5 years prior to start of study treatment
- Wide field radiotherapy ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug
- Active cardiac disease (e.g. Left Ventricular Ejection Fraction (LVEF) < 50%, QTcF > 480 msec on screening ECGelectrocardiogram (ECG), unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias)
- Inadequately controlled hypertension
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235
- Treatment at start of study treatment with drugs with a known risk to induce Torsades de Pointes, moderate and strong inhibitors or inducers of isoenzyme CYP3A4, warfarin and coumadin analogues, LHRH agonists
- History of photosensitivity reactions to other drugs
- Pregnant or nursing (lactating) woman
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BEZ235 BEZ235 -
- Primary Outcome Measures
Name Time Method Progression-free survival rate after 16 weeks of treatment 16 weeks after the first BEZ235 administration
- Secondary Outcome Measures
Name Time Method determine the efficacy of BEZ235 (objective response rate) about 6 months evaluate the clinical benefit rate of BEZ235 about 6 months evaluate the time to response about 6 months evaluate the Progression Free Survival Rate at 16-week & 24-week using the Kaplan-Meier method 16-week & 24-week after the first BEZ235 administration evaluate safety of BEZ235 (frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate) 30-35 days after treatment discontinuation