HR+, HER2- advanced breast cancer MedDRA version: 16.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: LEE011 200 mg
Product Code: LEE011 200 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LEE011
CAS Number: LEE011
Current Sponsor code: LEE011
Other descriptive name: LEE011
Co
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease. 2. Patient is postmenopausal. Postmenopausal status is defined either by: ? Prior bilateral oophorectomy ? Age ?60 ? Age =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. Patient who received any CDK4/6 inhibitor. 2. Patient who received any prior anti-cancer therapy (including chemotherapy) for advanced disease with the exception of surgery. Note: ? Patients who received (neo) adjuvant therapy for breast cancer are eligible. The disease free interval since the last adjuvant treatment must be greater than 12 months prior to randomization. Prior therapy with letrozole or anastrozole in the (neo) adjuvant setting is permitted if the disease free interval is greater than 12 months from the completion of treatment. 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. Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer. 5. 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) 90 at rest), PR interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec. ? Systolic blood pressure >160 or <90 mmHg Other exclusion criteria as defined by protocol may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival between LEE011 in combination with letrozole to placebo plus letrozole among postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease.;Secondary Objective: Key secondary: - To compare the two treatment arms with respect to overall survival. Other secondary: ? To evaluate the two treatment arms with respect to overall response rate and clinical benefit rate ? To evaluate the two treatment arms with respect to time to deterioration of ECOG performance status ? To evaluate the safety and tolerability of LEE011 in combination with letrozole ? To evaluate patient reported outcomes for health-related quality of life in the two treatment arms;Primary end point(s): Progression-free survival, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via local radiology assessment according to RECIST 1.1;Timepoint(s) of evaluation of this end point: up to approximately 25 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: - overall survival, defined as time from randomization to the date of death from any cause Other secondary: ? ORR, defined as proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST ? Clinical benefit rate (CBR), defined as the proportion of patients with a best overall repsonse of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1 ? time to definitive deterioration of ECOG performance status in one category of the score, defined as the time from date of randomization to the date of event, which is defined as at least one score lower than the baseline ? safety and tolerability of LEE001, determined by type, frequency and severity of Adverse Events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03 ? Time to definitive 10% deterioration in the global health status/QOL scale score of the EORTC QLQ-C30, defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause ? QTc interval, defined as time between the start of the Q wave and the of the T wave corrected for heart rate;Timepoint(s) of evaluation of this end point: OS: up to approximately 69 months ORR: up to approximately 25 months CBR: up to approximately 25 months ECOG performance status deterioration: up to approximately 25.5 months safety and tolerability: up to approximately 26 months 10% deterioration in QOL: up to approximately 25 months QTc interval: baseline, cycle 1 day 15, cycle 2 day 1 and cycle 3 day 1 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Norway, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed