E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 who progressed on or after mTORi. |
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E.1.1.1 | Medical condition in easily understood language |
addition of BKM120 to fulvestrant for treatment of patients with hormone receptor-positive HER2 negative locally advanced or metastatic breast cancer who progressed on or after mTOR inhibitors. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether treatment with BKM120 plus fulvestrant prolongs
PFS based on local investigator assessment compared to treatment with
placebo plus fulvestrant |
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E.2.2 | Secondary objectives of the trial |
Overall survival (OS) (key secondary)
Overall response rate (ORR)
Clinical benefit rate (CBR)
Type, frequency and severity of adverse events
Plasma concentration-time profiles of BKM120 - pharmacokinetics (PK)
Patient reported outcome for global health status/QoL
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
Other protocol defined criteria may apply |
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E.4 | Principal 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
Hypersensitivity to fulvestrant excipients
Certain scores on an anxiety and depression mood questionnaire given at screening
Other protocol defined criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS based on local investigator assessment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
OS
ORR
Clinical benefit rate
Type, frequency and severity of laboratory toxicities per CTCAEv4.03
Plasma concentration-time profiles of BKM120 given in combination with
fulvestrant and appropriate individual PK parameters based on
population PK model
Time to definitive 10% deterioration in the global health status/QOL
scale score of the EORTC QLQ-C30
Change from baseline in the global health status/QOL scale score of the
EORTC QLQ-C30
Time to definitive deterioration of the ECOG PS of the score of the
baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to approx. 21 months
Up to approx. 5.5 months
Up to approx. 5.5 months
at minimum at each study visit and up to approx. 8 months
C1D1, C1D15, C2D1,C3D1 and C4D1 (a cycle [C] = 4 weeks).
C1D1, C2D15, C4D1, then every 8 weeks until discontinuation (a cycle [C] = 4 weeks).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 129 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The End of Study is defined as the time point when data collection will stop and the final analysis of the study will occur. The End of Study will be declared depending on the results of the primary analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |