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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: BEZ235	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	March 2012
Estimated Primary Completion Date :	September 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: BEZ235	Drug: BEZ235

Outcome Measures

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Primary Outcome Measures :

1. Progression-free survival rate after 16 weeks of treatment [ Time Frame: 16 weeks after the first BEZ235 administration ]

Secondary Outcome Measures :

1. determine the efficacy of BEZ235 (objective response rate) [ Time Frame: about 6 months ]
2. evaluate the clinical benefit rate of BEZ235 [ Time Frame: about 6 months ]
3. evaluate the time to response [ Time Frame: about 6 months ]
4. evaluate the Progression Free Survival Rate at 16-week & 24-week using the Kaplan-Meier method [ Time Frame: 16-week & 24-week after the first BEZ235 administration ]
5. evaluate safety of BEZ235 (frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate) [ Time Frame: 30-35 days after treatment discontinuation ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals
Study Director:	Novartis Pharmaceuticals	Novartis Investigative Site

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01288092 History of Changes
Other Study ID Numbers:	CBEZ235B2201; 2010-024394-39 ( EudraCT Number )
First Posted:	February 2, 2011
Last Update Posted:	June 7, 2012
Last Verified:	June 2012

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Metastatic breast cancer; HER2 negative; HR positive	PI3K pathway; no more than 2 prior lines of chemotherapy; Metastatic Breast Cancer(MBC)

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases	Skin Diseases; Dactolisib; Antineoplastic Agents