BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Study of Orally Administered BEZ235 Monotherapy in Patients With Hormone Receptor Positive, HER2 Negative, Metastatic Breast Cancer, With or Without PI3K Activated Pathway

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: BEZ235


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEZ235<br> | Drug: BEZ235<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate after 16 weeks of treatment |  | 16 weeks after the first BEZ235 administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic breast cancer, HER2 negative, HR positive, PI3K pathway, no more than 2 prior lines of chemotherapy, Metastatic Breast Cancer(MBC)