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 weekly paclitaxel is effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer. |
|
E.1.1.1 | Medical condition in easily understood language |
addition of BKM120 to paclitaxel for treatment of patients with HER2- locally advanced or metastatic breast cancer |
|
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 | 14.1 |
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 |
|
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 assess the treatment effect of BKM120 once daily plus weekly paclitaxel versus BKM120 matching placebo once daily plus weekly paclitaxel on progression-free survival (PFS) |
|
E.2.2 | Secondary objectives of the trial |
To evaluate BKM120 once daily plus weekly paclitaxel versus BKM120 matching placebo once daily plus weekly paclitaxel with respect to
• Overall survival (OS)
• Overall response rate (ORR)
• Duration of response (DOR)
• Time to response
• Clinical benefit rate
• Safety
• To characterize the pharmacokinetics of BKM120 given in combination with paclitaxel
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Breast cancer that is locally advanced or metastatic
- HER2 negative disease, and a known 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
- Adequate bone marrow and organ function |
|
E.4 | Principal exclusion criteria |
- Prior chemotherapy for locally advanced or metastatic disease
- Previous treatment with PI3K inhibitors
- 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
- Sensitivity to paclitaxel treatment or inability to use the paclitaxel standard pre-treatment such as corticosteroids
- Pregnant or nursing (lactating) woman
- Certain scores on an anxiety and depression mood questionaire given at screening
Other protocol defined criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PFS in the PI3K pathway activated sub-population and full population. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
When a total of 125 PFS events have occurred (about 18-22 months); Estimated average 6-9 months for each patient. |
|
E.5.2 | 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)
- DOR, defined as time from the date of the first documented response (CR or PR, which has to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease as defined in Appendix 6 (RECIST 1.1)
- TTR, defined as the time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently)
- Clinical benefit rate 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 appropriate individual PK parameters based on population PK model , if deemed appropriate |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- until 1 year after the progression free survival analysis or 30 days after all patients stop treatment (about 3 years); approximately 1-3 years for each patient
- estimated 4-8 months for each patient
- estimated average 6-9 months for each patient
- estimated 4-8 months for each patient
- 24 weeks for each patient
- 30 days after treatment stops. Estimated 6-9 months for each patient
- Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1 |
|
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) | Yes |
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 | No |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Spain |
Peru |
Russian Federation |
Singapore |
South Africa |
Taiwan |
United Kingdom |
United States |
|
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
|
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. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |