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: 26 February 2018
• Main ID: EUCTR2011-005524-17-IT
• Date of registration: 03/09/2012
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA
• 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: 24/09/2012
• Target sample size: 842
• 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, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Peru, Russian Federation, Singapore, Slovakia, South Africa, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

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 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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 506
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 336

Exclusion criteria:
- Prior chemotherapy for locally advanced or metastatic disease - 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

Hormone receptor-positive HER2 negative locally advanced or metastatic breast cancer
MedDRA version: 15.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Product Name: NA
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
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: NA
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
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*IM 2SIR 5ML+2AGHI
Pharmaceutical Form: Solution for injection
INN or Proposed INN: FULVESTRANT
CAS Number: 129453-61-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

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

Primary end point(s): PFS in the PI3K pathway activated sub-population and full population.

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)

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

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)

2011-005524-17-GB

CBKM120F2302

Source(s) of Monetary Support

Novartis Pharma Services AG