Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor - Full Text View

Purpose

The purpose of this study is to determine wether the addition of daily BKM120 to fulvestrant is effective and safe in treating patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer refractory to aromatase inhibitor.

Condition	Intervention	Phase
Breast Cancer	Drug: BKM120 Matching placebo Drug: Fulvestrant Drug: BKM120	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Fulvestrant

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Progression free survival (PFS) [ Time Frame: up to approx. 8.3 months ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomisation.

Secondary Outcome Measures:

Overall survival (OS) [ Time Frame: up to approx. 32 months ] [ Designated as safety issue: No ]
Time from date of randomization to the date of death from any cause. Patients will be followed up for the duration of the study and for an expected average of every 3 months after end of treatment.
Overall response rate (ORR) [ Time Frame: up to approx. 8.3 months ] [ 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.Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomisation.
Clinical benefit rate (CBR) [ Time Frame: up to approx. 8.3 months ] [ 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. Patients will be followed up for the duration of the study and for an expected average of every 8 weeks after randomisation.
Type, frequency and severity of adverse events [ Time Frame: at minimum at each study visit and up to approx. 10 months ] [ Designated as safety issue: Yes ]
Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
Plasma concentration of BKM120 and Fulvestrant (Pharmacokinetics) [ Time Frame: Cycle 1 day 1, Cycle 1 day 15, cycle 2 day 1, cycle 2 day 2, cycle 2 day 15, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1 and cycle 6 day 1 ] [ Designated as safety issue: No ]
PK parameters; Patients will be assessed up to approx. 6 months after randomisation date. cycle = 28 days
Time profile of BKM120 and Fulvestrant (Pharmacokinetics) [ Time Frame: Cycle 1 day 1, Cycle 1 day 15, cycle 2 day 1, cycle 2 day 2, cycle 2 day 15, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1 and cycle 6 day 1 ] [ Designated as safety issue: No ]
PK parameters; Patients will be assessed up to approx. 6 months after randomisation date. cycle = 28 days
Patient reported outcomes for global health status/QOL [ Time Frame: Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment ] [ Designated as safety issue: No ]
Time to definitive deterioration in global health status/QOL; Change from baseline in global health status/Quality of Life (QOL). Patients will be assessed up to approx. 8.3 months

Estimated Enrollment:	1060
Study Start Date:	February 2012
Estimated Study Completion Date:	April 2017
Estimated Primary Completion Date:	March 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BKM120 and fulvestrant BKM120 100mg given daily and fulvestrant 500mg given intramuscularly at cycle 1 day 1, cycle 1 day 15 and at day 1 at each cycle thereafter. Treatment will be given until disease progression or as described in the protocol	Drug: Fulvestrant Fulvestrant 500mg given intramuscularly at cycle 1 day 1, cycle 1 day 15 and at day 1 at each cycle thereafter Drug: BKM120 BKM120 100mg, daily oral capsules
Active Comparator: Placebo and fulvestrant BKM120 matching placebo given daily and fulvestrant 500mg given intramuscularly at cycle 1 day 1, cycle 1 day 15 and at day 1 at each cycle thereafter. Treatment will be given until disease progression or as described in the protocol	Drug: BKM120 Matching placebo BKM120 matching placebo, daily oral Drug: Fulvestrant Fulvestrant 500mg given intramuscularly at cycle 1 day 1, cycle 1 day 15 and at day 1 at each cycle thereafter

Eligibility

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

Criteria

Inclusion Criteria:

Locally advanced or metastatic breast cancer
HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
Postmenopausal woman
A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment
Measurable disease or non measurable disease bone lesions in the absence of measurable disease as per RECIST 1.1
Adequate bone marrow and organ function defined by laboratory values

Exclusion Criteria:

Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
More than one prior chemotherapy line for metastatic disease
Symptomatic brain metastases
Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
Active heart (cardiac) disease as defined in the protocol
Certain scores on an anxiety and depression mood questionnaires
Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610284

Contacts

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

Show 326 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:	NCT01610284 History of Changes
Other Study ID Numbers:	CBKM120F2302, 2011-005524-17
Study First Received:	May 11, 2012
Last Updated:	May 22, 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) Brazil: ANVISA 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 Japan: Pharmaceuticals and Medical Devices Agency Greece: National Organization of Medicine China: Food and Drug Administration Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Thailand: Food and Drug Administration Germany: Federal Institute for Drugs and Medical Devices Canada: Health Canada South Africa: Department of Health Slovakia: State Institute for Drug Control Switzerland: Swissmedic Israel: Ministry of Health Peru: Ministry of Health

Keywords provided by Novartis:

Breast cancer
Hormone receptor positive
HER2-negative
Metastatic
Locally advanced

PI3K
Fulvestrant
Refractory
Aromatase inhibitor

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Estradiol
Fulvestrant
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Antineoplastic Agents, Hormonal
Estrogens
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013

Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor (BELLE-2)