Clinical trial NCT01288092: BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Metastatic breast cancer
HER2 negative
HR positive
PI3K pathway
no more than 2 prior lines of chemotherapy
Metastatic Breast Cancer(MBC)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-02-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival rate after 16 weeks of treatment
timeFrame: 16 weeks after the first BEZ235 administration
Secondary outcomes:
measure: determine the efficacy of BEZ235 (objective response rate)
timeFrame: about 6 months
measure: evaluate the clinical benefit rate of BEZ235
timeFrame: about 6 months
measure: evaluate the time to response
timeFrame: about 6 months
measure: evaluate the Progression Free Survival Rate at 16-week & 24-week using the Kaplan-Meier method
timeFrame: 16-week & 24-week after the first BEZ235 administration
measure: evaluate safety of BEZ235 (frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate)
timeFrame: 30-35 days after treatment discontinuation
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Investigative Site
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: