Advanced or Metastatic Breast Cancer
Conditions
Keywords
LEE011,, buparlisib,, letrozole,, HR +,, HER2 - negative,, post-menopausal,, breast cancer,, CDK 4/6,, PI3K,, MTD
Brief summary
This is a multi-center, open-label, non-randomized, phase I study
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease. 2. Patient is postmenopausal. 3. Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase. 4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory. 5. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. 6. Patient must have either: * Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion
Exclusion criteria
1. Patient who received any CDK4/6 or PI3K inhibitor. 2. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following: * History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Documented cardiomyopathy * Patient has a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) * History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months. * On screening, any of the following cardiac parameters: bradycardia (heart rate \< 50 at rest), tachycardia (heart rate \> 90 at rest), PR interval \> 220 msec, QRS interval \>109 msec, or QTcF \>450 msec. Systolic blood pressure \>160 or \<90 mmHg 3. Patient is currently receiving any of the following medications: * That are known strong inducers or inhibitors of CYP3A4. * That have a known risk to prolong the QT interval or induce Torsades de Pointes. * That have a narrow therapeutic window and are predominantly metabolized through CYP3A4. 4. Certain scores on an anxiety and depression mood questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs) | 28 days | Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle |
| Safety and tolerability of the combination of LEE011, buparlisib, and letrozole | approximately 25 months | Dose Expansion Phase: Incidence of AEs, SAEs (overal and severity), laboratory abnormalities, ECG, vital, dose interteruptions, dose reductions, and dose intensity as a measure of safety and tolerability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS (progression free survival) | approximately 25 months | Dose Expansion Phase: Time from date of start of treatment to date of first documented progression or death due to any cause. |
| Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole | approximately 25 months | Dose Escalation Phase: Incidence of AEs, SAEs (overall and severity), laboratory abnormalities, ECG, vital, dose interterruptions, dose reductions, and dose intensity as a measure of safety and tolerability. |
| Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles | approximately 25 months | Dose Escalation Phase: When given in combination as well any other clinically significant metabolites that may be identified |
| Disease control rate | approximately 25 months | Dose Expansion Phase: Proportion of patients with the best overall response of CR (complete response), PR (partial response), or SD (stable disease) |
Countries
Spain, United States
Outcome results
None listed