a pharmacodynamics pre-surgical study of lee011 in early breast cancer patients (monaleesa-1)

Conditions: Early Breast Cancer

Summary: this is a multi-center, open-label phase ii randomized pre-surgical pharmacodynamics study.

this randomized pre-surgical pharmacodynamics study will assess the biological activity of lee011 plus letrozole versus single agent letrozole in primary breast cancer.

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 \ 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

Keywords: hr-positive her2-negative breast cancer lee011 letrozole cdk cdk4 cdk6 cdk4/6 pharmacodynamics pre-surgical postmenopausal