- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01919229
A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1) (MONALEESA-1)
November 30, 2015 updated by: Novartis Pharmaceuticals
A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer
This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Singapore, Singapore, 169610
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Barcelona, Catalunya, Spain, 08003
- Novartis Investigative Site
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Arkansas
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Fayetteville, Arkansas, United States, 72703
- Highlands Oncology Group SC
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California
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Los Angeles, California, United States, 90095
- University of California at Los Angeles UCLA SC
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital SC-9
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Texas
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Houston, Texas, United States, 77030-4009
- University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Letrozole
Letrozole 2.5 mg alone once daily
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Letrozole was supplied in 2.5mg tablets for oral use.
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Experimental: LEE011 400 mg + letrozole
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
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Letrozole was supplied in 2.5mg tablets for oral use.
Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.
Other Names:
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Experimental: LEE011 600mg + letrozole
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
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Letrozole was supplied in 2.5mg tablets for oral use.
Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cell Cycle Response Rate Per Cell Proliferation Marker Ki67
Time Frame: Day 1, Day15
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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.
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Day 1, Day15
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of the Combination
Time Frame: Up to 30 days after the last dose
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Occurrence, frequency and severity of adverse events (AEs), laboratory abnormalities
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Up to 30 days after the last dose
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Change From Baseline in Electrocardiogram (ECG) Parameters
Time Frame: Baseline, Day 14
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Baseline, Day 14
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Change From Baseline in Expression of Retinoblastoma Protein (pRB)
Time Frame: Baseline, Day 15
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Baseline, Day 15
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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
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Days 1, 8, 14 and 15
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Change in ECG Morphology
Time Frame: Baseline, Day 14
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Baseline, Day 14
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Correlation Between PK Concentrations and ECG Changes
Time Frame: Day 14
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Correlation between the QTc interval change from baseline and plasma concentrations of LEE011 and/or any relevant metabolites
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Day 14
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Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1)
Time Frame: Baseline, Day 15
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Baseline, Day 15
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2013
Primary Completion (Actual)
September 1, 2014
Study Completion (Actual)
September 1, 2014
Study Registration Dates
First Submitted
August 2, 2013
First Submitted That Met QC Criteria
August 6, 2013
First Posted (Estimate)
August 8, 2013
Study Record Updates
Last Update Posted (Estimate)
January 1, 2016
Last Update Submitted That Met QC Criteria
November 30, 2015
Last Verified
November 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Letrozole
Other Study ID Numbers
- CLEE011A2201
- 2013-002588-24 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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