Metastatic Breast Cancer
Conditions
Keywords
Metastatic breast cancer, HER2 negative, HR positive, PI3K pathway, no more than 2 prior lines of chemotherapy, Metastatic Breast Cancer(MBC)
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.
Interventions
DRUGBEZ235
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival rate after 16 weeks of treatment | 16 weeks after the first BEZ235 administration |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Outcome results
None listed