estrogen receptor positive, Her2- locally advanced or metastatic breast cancer
Conditions
Interventions
Product Code: LEE011
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LEE011
CAS Number: LEE011
Current Sponsor code: LEE011
Other descriptive name: LEE011
Concentration unit: mg milligram(s)
C
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult women (? 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy - Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer - A representative tumor specimen must be available for molecular testing. An archival tumor sample may be submitted; if one is not available, a newly obtained tumor specimen must be submitted instead - Postmenopausal women. Postmenopausal status is defined either by: - Age ? 18 with prior bilateral oophorectomy - Age ? 60 years - Age =65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: - Her2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive). - Patients who received more than one chemotherapy line for advanced breast cancer. - Previous treatment with CDK4/6 inhibitors, exemestane or mTOR inhibitors*. - History of active or symptomatic brain or other CNS metastases. - Impaired cardiac function or clinically significant cardiac diseases, including any of the following: - Left ventricular ejection fraction (LVEF) 470 ms for females on screening ECG - Any other clinically significant heart disease such as angina pectoris, resting bradycardia, left bundle branch block, ventricular tachyarrhythmia, unstable atrial fibrillation, Right bundle branch block with left anterior hemiblock (bifascicular block), acute myocardial infarction or any heart disease that requires the use of a cardiac pacemaker or implantable cardioverter defibrillator ? 3 months prior to starting study drug. - Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans. - Patients who are currently receiving treatment (within five days prior to randomization) with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window. Agents that are known strong inducers or inhibitors CYP3A4 are prohibited Exceptions for Phase Ib patients: a. Patients who received more than two prior lines of chemotherapy are eligible b. Patients who received CDK4/6 inhibitors, exemestane or mTOR inhibitors are eligible
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary purpose of the phase Ib part of this study is to determine the maximum tolerated dose(s) (MTD(s)) and/or recommended phase II dose (RP2D) of LEE011 + everolimus + exemestane in patients with ER+ Her2- advanced breast cancer. The phase II part of the study will evaluate the triple combination of LEE011 + everolimus + exemestane and the double combination of LEE011 + exemestane in comparison to everolimus + exemestane.;Secondary Objective: Safety, tolerability, and PK of the LEE011 + exemestane, LEE011 + everolimus + exemestane combinations will be assessed.;Primary end point(s): 1. Incidence of dose limiting toxicity (DLT)- Phase Ib 2. Progression Free Survival (PFS)- Phase II;Timepoint(s) of evaluation of this end point: 1. Day 1- Day 28 of Cycle 1 (28 day cycle) 2. Approximately 26 months after FPFV | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Incidence of adverse drug reactions 2. Incidence of serious adverse events 3. Plasma concentration-time profiles - Phase Ib/II 4. Overall Response Rate (ORR)- Phase Ib and Phase II 5. Duration Of Response (DOR) - Phase Ib, Phase II 6. Overall survival (OS) - Phase II 7. Plasma concentration -time profiles: AUCtau, Cmin, Cmax, Tmax, Racc - Phase Ib/II 8. Disease Control Rate (DCR) - Phase Ib, Phase II;Timepoint(s) of evaluation of this end point: 1-2. Every cycle (1 cycle = 28 days) until study evlauation completion visit 3 and 7. 6 cycles of treatment (28-day cycles) 4-6 and 8. Approximately 26 months after FPFV | — |
Countries
Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Netherlands, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed