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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01288092
• Other study ID #: CBEZ235B2201
• Secondary ID: 2010-024394-39
• Status: Withdrawn
• Phase: Phase 2
• First received: January 19, 2011
• Last updated: June 5, 2012
• Start date: March 2012

Study information

• Verified date: June 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaChina: Food and Drug AdministrationColumbia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesHong Kong: Department of HealthHungary: National Institute of PharmacyItaly: National Institute of HealthJapan: Pharmaceuticals and Medical Devices AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Peru: Ministry of HealthRussia: Ministry of Health of the Russian FederationSingapore: Health Sciences AuthoritySpain: Spanish Agency of MedicinesSouth Africa: Department of HealthSweden: Medical Products AgencyTaiwan: Department of HealthThailand: Food and Drug AdministrationTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• BEZ235

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival rate after 16 weeks of treatment		16 weeks after the first BEZ235 administration	No
Secondary	determine the efficacy of BEZ235 (objective response rate)		about 6 months	No
Secondary	evaluate the clinical benefit rate of BEZ235		about 6 months	No
Secondary	evaluate the time to response		about 6 months	No
Secondary	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	No
Secondary	evaluate safety of BEZ235 (frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate)		30-35 days after treatment discontinuation	No