BOOG 2014-01

General Information

BOOG number

BOOG 2014-01




Date: 30/01/2015

Inclusion closed


Full title

A randomized double-blind, placebo-controlled study of LEE011 in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease




Target sample size


Actual accrual

671 (NL: 24)
Date: 23/02/2015




Principal Investigator(s)

G. Sonke

Study manager

G. Frans (Novartis), J.M. Rademaker-Lakhai (BOOG)

Central datamanagement and randomization





Primary: To compare progression free survival between LEE011 in combination with letrozole to placebo with letrozole among postmenopausal women with HR+, HER2-negative advanced breast cancer who received no prior therapy for advanced disease using RECIST 1.1. Key Secondary: To compare the two treatment arms with respect to overall survival. Secondary Objectives To evaluate the two treatment arms with respect to overall respons rate by RECIST 1.1 and clinical benefit rate as the percentage of patients with complete response, partial response, or stable disease lasting 24 weeks or longer per RECIST 1.1. 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 as measured by frequency/severity of adverse events and laboratory abnormalities. To evaluate patient reported outcomes for health-related quality of life in the two treatment arms as time to definitive 10% deterioration and change form baseline in the global health status/ quality of life scale score of the EORTC QLQ-C30.


Primary endpoint: Progression-free survival using RECIST 1.1 criteria, as assessed by local radiologists/investigators. Key secondary endpoint: Overall-survival. Other secondary endpoints: ORR, ECOG PS, safety and tolerability of LEE011, Change from baseline in the global health status/QOL scale score of the EORTC QLQ-C30

Eligibility 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 <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. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory. 4. 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. 5. 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 6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion criteria 1. Patient who received any CDK4/6 inhibitor. 2. Patients with locally advanced (unresectable) or inflammatory breast cancer. Patients who received adjuvant therapy for breast cancer are eligible. The treatment free interval since the last adjuvant treatment must be at least 12 months prior to randomization. Prior therapy with letrozole in the adjuvant setting is permitted if the patient did not have progressive disease while on letrozole. 3. 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. 4. 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 5. 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 known risk to prolong the QT interval or induce Torsades de Pointes. That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.

Regulatory Information

CCMO approval


EC approval


EudraCT number