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A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1) (MONALEESA-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01919229
Recruitment Status : Terminated (Due to low recruitment, it was decided to terminate the study.)
First Posted : August 8, 2013
Results First Posted : January 1, 2016
Last Update Posted : January 1, 2016
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Early Breast Cancer Drug: LEE011 (ribociclib) Drug: letrozole Phase 2

Detailed Description:
This randomized pre-surgical pharmacodynamics study will assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer
Study Start Date : October 2013
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Letrozole
Letrozole 2.5 mg alone once daily
Drug: letrozole
Letrozole was supplied in 2.5mg tablets for oral use.

Experimental: LEE011 400 mg + letrozole
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
Drug: LEE011 (ribociclib)
Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.
Other Name: ribociclib

Drug: letrozole
Letrozole was supplied in 2.5mg tablets for oral use.

Experimental: LEE011 600mg + letrozole
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
Drug: LEE011 (ribociclib)
Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.
Other Name: ribociclib

Drug: letrozole
Letrozole was supplied in 2.5mg tablets for oral use.

Primary Outcome Measures :
  1. Cell Cycle Response Rate Per Cell Proliferation Marker Ki67 [ Time Frame: Day 1, Day15 ]
    Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.

Secondary Outcome Measures :
  1. Safety and Tolerability of the Combination [ Time Frame: Up to 30 days after the last dose ]
    Occurrence, frequency and severity of adverse events (AEs), laboratory abnormalities

  2. Change From Baseline in Electrocardiogram (ECG) Parameters [ Time Frame: Baseline, Day 14 ]
  3. Change From Baseline in Expression of Retinoblastoma Protein (pRB) [ Time Frame: Baseline, Day 15 ]
  4. PK (Pharmacokinetics) Parameters, Including But Not Limited to, Cmax, Tmax, AUClast for LEE011 (and Any Relevant Metabolites) and Letrozole. [ Time Frame: Days 1, 8, 14 and 15 ]
  5. Change in ECG Morphology [ Time Frame: Baseline, Day 14 ]
  6. Correlation Between PK Concentrations and ECG Changes [ Time Frame: Day 14 ]
    Correlation between the QTc interval change from baseline and plasma concentrations of LEE011 and/or any relevant metabolites

  7. Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1) [ Time Frame: Baseline, Day 15 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01919229

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United States, Arkansas
Highlands Oncology Group SC
Fayetteville, Arkansas, United States, 72703
United States, California
University of California at Los Angeles UCLA SC
Los Angeles, California, United States, 90095
United States, Massachusetts
Massachusetts General Hospital SC-9
Boston, Massachusetts, United States, 02114
United States, Texas
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)
Houston, Texas, United States, 77030-4009
Novartis Investigative Site
Singapore, Singapore, 169610
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08003
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT01919229     History of Changes
Other Study ID Numbers: CLEE011A2201
2013-002588-24 ( EudraCT Number )
First Posted: August 8, 2013    Key Record Dates
Results First Posted: January 1, 2016
Last Update Posted: January 1, 2016
Last Verified: November 2015
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs