Study of efficacy and safety of LEE011 in postmenopausal women with advanced breast cancer.

Conditions: HR+, HER2- advanced breast cancer
MedDRA version: 16.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-003084-61-IT

Lead Sponsor: ovartis Pharma

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 500

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 <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range
Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status. Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression in this trial.
3. No prior systemic anti-cancer therapy for advanced disease.
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
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Other inclusion criteria as defined by protocol may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

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) < 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