A phase III study of BKM120 with fulvestrant in postmenopausal patients with hormone receptor + HER2-locally advanced or metatstatic breast cancer refractory to aromatase inhibitors

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2011-005524-17-SK
• Date of registration: 27/08/2015
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: A phase III study of BKM120 with fulvestrant in postmenopausal patients with hormone receptor + HER2-locally advanced or metatstatic breast cancer refractory to aromatase inhibitors
• Scientific 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. - BELLE 2
• Date of first enrolment: 28/11/2012
• Target sample size: 1200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005524-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Democratic People's Republic of, Korea, Republic of, Netherlands, Peru, Poland, Russian Federation, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desl
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desl
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
- Breast cancer that is locally advanced or metastatic
- HER2 negative disease, hormone receptor positive status (common breast cancer classification tests)
- postmenopausal woman
- A tumor sample must be shipped to novartis designed laboratory for identification of biomarkers (PI3K activation status)
- Progression recurrence of breast cancer hile on after aromatase inhibitor treatment
- Measurable disease or non measurable disease bone lesions lytic or mixed in the absence of measurable disease as per RECIST 1.1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitors, fulvestrant
- More than one prior chemotherapy line for metastatic disease
- 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
- Certain scores on an anxiety and depression mood questionaire given at screening
Other protocol defined criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

This study will evaluate whether 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.
MedDRA version: 18.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: BKM120
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: buparlisib
CAS Number: not known
Current Sponsor code: BKM120
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: BKM120
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: buparlisib
CAS Number: not known
Current Sponsor code: BKM120
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Faslodex
Product Name: fulvestrant
Pharmaceutical Form: Solution for injection
INN or Proposed INN: FULVESTRANT
CAS Number: 129453-61-8
Current Sponsor code: fulvestrant
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: To evaluate BKM120 once daily plus fulvestrant versus BKM120 matching placebo once daily plus fulvestrant with respect to
• Overall survival (OS)
• Overall response rate (ORR)
• Clinical benefit rate (CBR)
Safety
• To characterize the pharmacokinetics of BKM120 given in combination with fulvestrant
Patients health related quality of life

Main Objective: To assess the treatment effect of BKM120 once daily plus fulvestrant versus BKM120 matching placebo once daily plus fulvestrant on progression-free survival (PFS)

Timepoint(s) of evaluation of this end point: every 6 weeks after randomisation and then every 8 weeks

Primary end point(s): To determine whether treatment with PFS in the main study cohort (known PI3K status) regardless of the PI3K pathway activation status and / or full population (main study cohort + PI3K unknown ) (full population) or PI3K pathway activated sub-population.

Secondary Outcome(s)

Secondary end point(s): - OS, defined as time from date of randomization to the date of death from any cause
- ORR, defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) as defined in Appendix 6 (RECIST 1.1)
- Clinical benefit rate (CBR) is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in Appendix 6 (RECIST 1.1)
- Safety: Type, frequency and severity of adverse events per CTCAEv4.03; type, frequency and severity of laboratory toxicities per CTCAEv4.03
- Summary statistics for PK: plasma concentration-time profiles of BKM120 and fulvestrant appropriate PK parameters

Timepoint(s) of evaluation of this end point: - every 3 months after end of treatment OS
- estimated 8 weeks after randomisation ORR
- estimated 8 weeks after randomisation CBR
- contiuous safety
- at each cycle specific days defined in protocol

Secondary ID(s)

CBKM120F2302

2011-005524-17-GB

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact: