A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation - Full Text View

Purpose

This study will evaluate whether the addition of daily BKM120 to weekly paclitaxel is effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: Paclitaxel Drug: BKM120 matching placebo Drug: BKM120	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Placebo Controlled, Phase II Study of BKM120 Plus Paclitaxel in Patients With HER2 Negative Inoperable Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Pathway Activation.

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

progression free survival (PFS) [ Time Frame: Every 8 weeks after randomization ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment

Secondary Outcome Measures:

overall survival [ Time Frame: Every 3 months after end of Treatment ] [ Designated as safety issue: No ]
Time from date of randomization to the date of death from any cause
overall response rate [ Time Frame: Every 8 weeks after randomization ] [ Designated as safety issue: No ]
Proportion of patients with best overall response of complete response (CR) or partial response (PR) based according to RECIST 1.1
duration of response [ Time Frame: Every 8 weeks after randomization ] [ Designated as safety issue: No ]
time from the date of the first documented response (CR or PR, which has to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease
time to response [ Time Frame: Every 8 weeks after randomization ] [ Designated as safety issue: No ]
time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).
clinical benefit rate [ Time Frame: Every 8 weeks after randomization ] [ Designated as safety issue: No ]
Proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1.
Type, frequency and severity of adverse events [ Time Frame: Continuous, until 30 days after treatment stops ] [ Designated as safety issue: Yes ]
Safety will be determine by type, frequency and severity of adverse events per CTCAEv4.03 Type, frequency and severity of laboratory toxicities per CTCAEv4.03
Plasma concentration-time profiles of BKM120 - pharmacokinetics (PK) [ Time Frame: Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1. ] [ Designated as safety issue: No ]
Summary statistics for PK: plasma concentration-time profiles of BKM120 and appropriate individual PK parameters based on population PK model , if deemed appropriate; each cycle = 28 days

Estimated Enrollment:	200
Study Start Date:	August 2012
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BKM120 and paclitaxel BKM120 100 mg per day and paclitaxel 80 mg/m2 per week, given until progression or as described in the protocol.	Drug: BKM120 BKM120 daily oral capsules
Active Comparator: Placebo and paclitaxel BKM120 matching placebo daily and paclitaxel 80 mg/m2 per week, given until progression or as described in the protocol.	Drug: Paclitaxel intravenous paclitaxel 80 mg/m2 per week. Other Name: Taxol Drug: BKM120 matching placebo BKM120 matching placebo, daily oral capsules

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Breast cancer that is locally advanced or metastatic
HER2 negative disease, and a known hormone receptor status (common breast cancer classification tests)
A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
Adequate bone marrow and organ function

Exclusion Criteria:

Prior chemotherapy for locally advanced or metastatic disease
Previous treatment with PI3K inhibitors
Symptomatic brain metastases
Concurrent malignancy or malignancy within 3 years prior to start of study treatment
Certain drugs or radiation within 2-4 weeks of enrollment
Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
Active heart (cardiac) disease as defined in the protocol
Sensitivity to paclitaxel treatment or inability to use the paclitaxel standard pre-treatment such as corticosteroids
Pregnant or nursing (lactating) woman
Certain scores on an anxiety and depression mood questionaire given at screening
Other protocol defined criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01572727

Contacts

Contact: Novartis Pharmaceuticals	1-888-669-6682
Contact: Novartis Pharmaceuticals

Show 103 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01572727 History of Changes
Other Study ID Numbers:	CBKM120F2202, 2011-005932-24
Study First Received:	April 4, 2012
Last Updated:	May 16, 2013
Health Authority:	United States: Food and Drug Administration Austria: Agency for Health and Food Safety Belgium: Federal Agency for Medicinal Products and Health Products Czech Republic: State Institute for Drug Control Spain: Spanish Agency of Medicines France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Hungary: National Institute of Pharmacy Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Hong Kong: Department of Health Brazil: ENVISA Italy: National Institute of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency South Korea: Korea Food and Drug Administration (KFDA) Russia: Ministry of Health of the Russian Federation Singapore: Health Sciences Authority Taiwan : Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Novartis:

BKM120
paclitaxel
breast cancer
metastatic

locally advanced
PI3K
PIK3CA
PTEN

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Tubulin Modulators

Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013

A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation (BELLE-4)