Description:
This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to
determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo
plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human
epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor
(AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or
after mammalian target of rapamycin inhibitor (mTORi)-based treatment.
Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in
combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg.
Randomization was stratified according to visceral disease status (present or absent).
Title
- Brief Title: 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
- 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
Clinical Trial IDs
- ORG STUDY ID:
CBKM120F2303
- SECONDARY ID:
2012-002571-34
- NCT ID:
NCT01633060
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Fulvestrant | | BKM120 and fulvestrant |
| BKM120 | | BKM120 and fulvestrant |
| BKM120 matching placebo | | Placebo and fulvestrant |
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| BKM120 and fulvestrant | Experimental | BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol test. | |
| Placebo and fulvestrant | Active Comparator | BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. | - Fulvestrant
- BKM120 matching placebo
|
Eligibility 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
- Acute viral hepatitis or history of chronic or acute HBV, HCV, HAV, HDV, HEV
- Other protocol defined criteria may apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Up to approx. 5.5 months |
| Safety Issue: | |
| Description: | 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
| Measure: | Overall survival (OS) |
| Time Frame: | Up to approx. 21 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall response rate (ORR) |
| Time Frame: | Up to approx. 5.5 months |
| Safety Issue: | |
| Description: | Proportion of patients, in the full population and by PIK3CA mutational status based on ctDNA, 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. |
| Measure: | Clinical benefit rate (CBR) |
| Time Frame: | Up to approx. 5.5 months |
| Safety Issue: | |
| Description: | Proportion of patients, in the full population and by PIK3CA mutational status based on ctDNA, with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or non-CR/non-PD lasting more than 14 weeks. CBR 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. |
| Measure: | Type, frequency and severity of adverse events |
| Time Frame: | at minimum at each study visit and up to approx. 8 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Plasma concentration-time profiles of BKM120 - pharmacokinetics (PK) |
| Time Frame: | C1D1, C1D15, C2D1,C3D1 and C4D1 (a cycle [C] = 4 weeks), D = Day |
| Safety Issue: | |
| Description: | Plasma concentration-time profiles of BKM120 and appropriate individual PK parameters. |
| Measure: | Patient reported outcome for global health status/QoL |
| Time Frame: | C1D1, C2D15, C4D1, then every 8 weeks until discontinuation (a cycle [C] = 4 weeks). |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression Free Survival (PFS) in PIK3CA mutational status |
| Time Frame: | Up to approx. 5.5 months |
| Safety Issue: | |
| Description: | PFS by PIK3CA mutational status based on ctDNA assessment 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. Patient will be followed up to the duration of the study and for an expected avrage of every 6wks after randomization |
| Measure: | Overall survival (OS) in PIK3CA mutational status |
| Time Frame: | Up to approx. 21 months |
| Safety Issue: | |
| Description: | OS by PIK3CA mutational status based on ctDNA is defined as the 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- BKM120
- fulvestrant
- breast cancer
- metastatic
- locally advanced
- AI treated
- mTOR inhibitor
- PI3K
- PIK3CA
- PTEN
- HER2-
- HR+
Last Updated
September 12, 2017
