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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: BEZ235

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BEZ235	Drug: BEZ235

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Investigative Site

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: January 19, 2011
• First Submitted That Met QC Criteria: January 31, 2011
• First Posted (Estimate): February 2, 2011

Study Record Updates

• Last Update Posted (Estimate): June 7, 2012
• Last Update Submitted That Met QC Criteria: June 5, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: HER2 negative; Metastatic breast cancer; HR positive; PI3K pathway; no more than 2 prior lines of chemotherapy; Metastatic Breast Cancer(MBC)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Dactolisib
• Other Study ID Numbers: CBEZ235B2201; 2010-024394-39 (EudraCT Number)