Trial record 1 of 1 for:    NCT01633060
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A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi (BELLE-3)

This study is currently recruiting participants.
Verified March 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01633060
First received: June 29, 2012
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

This study will evaluate whether the addition of daily BKM120 to fulvestrant is effective and safe in treating patients with HR+, HER2-, AI treated locally advanced or metastatic breast cancer who progressed on or after mTor inhibitor based treatment.


Condition Intervention Phase
Metastatic Breast Cancer HR+, HER2-
Drug: Fulvestrant
Drug: BKM120
Drug: BKM120 matching placebo
Phase 3

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 Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibitor Based Treatment

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Up to approx. 5.5 months ] [ Designated as safety issue: No ]
    PFS is defined as time from 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. Patients will be followed up for the duration of the study and for an expected average of every 6 weeks after randomization.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to approx. 21 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. 5.5 months ] [ Designated as safety issue: No ]
    Proportion of patients with best overall response of complete response (CR) or partial response (PR). ORR will be assessed according to RECIST 1.1 criteria. Patients will be followed up for the duration of the study and for an expected average of every 6 weeks after randomization.

  • Clinical benefit rate (CBR) [ Time Frame: Up to approx. 5.5 months ] [ Designated as safety issue: No ]
    Proportion of patients with best overall response of complete response (CR) or partial response (PR). ORR will be assessed according to RECIST 1.1 criteria. Patients will be followed up for the duration of the study and for an expected average of every 6 weeks after randomization.

  • Type, frequency and severity of adverse events [ Time Frame: at minimum at each study visit and up to approx. 8 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-time profiles of BKM120 - pharmacokinetics (PK) [ Time Frame: C1D1, C1D15, C2D1,C3D1 and C4D1 (a cycle [C] = 4 weeks), D = Day ] [ Designated as safety issue: No ]
    Plasma concentration-time profiles of BKM120 and appropriate individual PK parameters.

  • Patient reported outcome for global health status/QoL [ Time Frame: C1D1, C2D15, C4D1, then every 8 weeks until discontinuation (a cycle [C] = 4 weeks). ] [ Designated as safety issue: No ]
    Time to definitive deterioration in the global health status/QoL scale score. Change from baseline in the global health status/QOL scale score. Patients will be assessed up to approx. 5.5 months.


Estimated Enrollment: 420
Study Start Date: October 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BKM120 and fulvestrant
BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol test.
Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (cycle 1 days 1 & 15 and once every cycle thereafter)
Drug: BKM120
BKM120 100 mg once daily
Active Comparator: Placebo and fulvestrant
BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Drug: Fulvestrant
Intramuscular fulvestrant 500 mg (cycle 1 days 1 & 15 and once every cycle thereafter)
Drug: BKM120 matching placebo
BKM120 matching placebo, once daily

  Eligibility

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

Inclusion Criteria:

  • Postmenopausal women
  • Breast cancer that is locally advanced or metastatic
  • HER2 negative disease, and a known positive 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
  • Prior treatment with AIs
  • Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry
  • Adequate bone marrow and organ function

Exclusion Criteria:

  • More than 1 prior chemotherapy given for locally advanced or metastatic disease
  • Previous treatment with PI3K inhibitors, AKT inhibitors or fulvestrant
  • Symptomatic CNS 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 or a history of cardiac dysfunction as defined in the protocol
  • Hyper sensitivity to fulvestrant treatment excipients
  • Certain scores on an anxiety and depression mood questionnaire given at screening
  • Other protocol defined criteria may apply
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01633060

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

  Show 244 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01633060     History of Changes
Other Study ID Numbers: CBKM120F2303, 2012-002571-34
Study First Received: June 29, 2012
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Finland: Finnish Medicines Agency
France: ANSM - French Health Products Safety Agency
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Italy: National Institute of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Thailand: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
BKM120
fulvestrant
breast cancer
metastatic
locally advanced
AI treated
mTOR inhibitor
PI3K
PIK3CA
PTEN

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Sirolimus
Everolimus
Fulvestrant
Estradiol
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Estrogens
Hormones

ClinicalTrials.gov processed this record on April 16, 2014