A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)
Condition: Early Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: LEE011 (ribociclib); letrozole
Intervention description: Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.; Letrozole was supplied in 2.5mg tablets for oral use.
Intervention MeSH terms: Letrozole
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HR-positive; HER2-negative; Breast cancer; LEE011; Letrozole; CDK; CDK4; CDK6; CDK4/6; Pharmacodynamics; Pre-surgical; Postmenopausal

Summary:

      This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female patient is ≥ 18 years old at the time of informed consent, with newly diagnosed
             resectable breast cancer, who received no prior therapy for breast cancer

          -  Patient is postmenopausal. Postmenopausal status is defined either by:

               -  Prior bilateral oophorectomy

               -  Age ≥60

               -  Age <60 and amenorrhea for 12 or more months and FSH (Follicle Stimulating
                  Hormone) and estradiol in the postmenopausal range.

          -  Patient has a histologically (and/or cytologically) confirmed diagnosis of
             estrogen-receptor positive and/or progesterone receptor positive breast cancer by
             local laboratory.

          -  Patient has a grade II or grade III invasive breast cancer

          -  Patient has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer
             defined as a negative in situ hybridization test or an Immunohistochemistry (IHC)
             status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization (respectively
             FISH/CISH/SISH) test is required) by local laboratory testing

          -  Patient has at least one breast lesion with a diameter of ≥1.0 cm by the most accurate
             imaging modality used.

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

        Exclusion Criteria:

          -  Patient has received any prior therapy for breast cancer.

          -  Patient has a concurrent malignancy or malignancy within 3 years of randomization,
             with the exception of adequately treated, basal cell skin cancer or squamous cell
             carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.

          -  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 ventricular, supraventricular, nodal arrhythmias, or any other cardiac
                  arrhythmias, Long QT Syndrome or conduction abnormality in the previous 12
                  months.

               -  Family history of QTc prolongation or of unexplainable sudden death at <50 years
                  of age.

               -  On screening 12 lead ECG, 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 mmHg or <90 mmHg.

          -  Patient is currently receiving any of the following medications (see

        Appendix 1 for details):

          -  That are known strong inducers or inhibitors of CYP3A4.

          -  That have a narrow therapeutic window and are predominantly metabolized through
             CYP3A4.

          -  That have a known risk to prolong the QT interval or induce Torsades de Pointes.

        Other protocol-defined inclusion/exclusion criteria may apply