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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01610284
First received: May 11, 2012
Last updated: August 14, 2014
Last verified: August 2014

May 11, 2012
August 14, 2014
August 2012
September 2017   (final data collection date for primary outcome measure)
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.
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. Patients will be assessed
Complete list of historical versions of study NCT01610284 on ClinicalTrials.gov Archive Site
  • 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
  • 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 causPatients 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
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Breast Cancer
  • 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
  • Drug: BKM120
    BKM120 100mg, daily oral capsules
  • 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
    Interventions:
    • Drug: Fulvestrant
    • Drug: BKM120
  • 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
    Interventions:
    • Drug: BKM120 Matching placebo
    • Drug: Fulvestrant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1200
September 2017
September 2017   (final data collection date for primary outcome measure)

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

Female
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   China,   Spain,   United Kingdom,   Thailand,   Taiwan,   Switzerland,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Czech Republic,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Peru,   Poland,   Russian Federation,   Singapore,   Slovakia,   South Africa
 
NCT01610284
CBKM120F2302, 2011-005524-17
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP