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Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2) (MONALEESA-2)

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: NCT01958021
Recruitment Status : Completed
First Posted : October 8, 2013
Results First Posted : May 12, 2017
Last Update Posted : April 26, 2023
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a multi-center, randomized, double-blinded, placebo controlled trial.

Condition or disease Intervention/treatment Phase
Advanced, Metastatic Breast Cancer Drug: LEE011 Drug: Letrozole Drug: LEE011 Placebo Phase 3

Detailed Description:
The primary purpose of this study was to assess the efficacy of LEE011, as measured by progression free survival (PFS), in postmenopausal women with HR positive, HER2 negative advanced breast cancer who received no prior treatment for advanced disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 668 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : December 17, 2013
Actual Primary Completion Date : January 29, 2016
Actual Study Completion Date : March 16, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: LEE011 + letrozole
LEE011 (Ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD
Drug: LEE011
Ribociclib was administered orally at a dose of 600 mg once daily (three 200 mg capsules).

Drug: Letrozole
Letrozole 2.5 mg tablets taken orally.

Placebo Comparator: Placebo + letrozole
Matching ribociclib placebo was the control drug and was administered orally once daily.
Drug: Letrozole
Letrozole 2.5 mg tablets taken orally.

Drug: LEE011 Placebo
Matching ribociclib placebo was the control drug and was administered orally once daily.

Primary Outcome Measures :
  1. Progression Free Survival (PFS) Per Investigator Assessment [ Time Frame: Up to approximately 20 months ]
    PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) as Per Investigator Assessment [ Time Frame: Up to approximately 20 months ]
    Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  2. Overall Survival (OS) [ Time Frame: Up to approximately 65 months ]
    Time from date of randomization to the date of death from any cause.

  3. Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 20 months ]
    Clinical Benefit Rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1.

  4. Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score [ Time Frame: Up to approximately 20.5 months ]
    Time to definitive deterioration of ECOG performance status in one category of score is defined as the time from the date of randomization to the date of event, which is defined as at least one score lower than the baseline.

  5. Safety and Tolerability of LEE011 [ Time Frame: Up to approximately 21 months ]
    Safety will be determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03.

  6. Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximately 20 months ]
    The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause.

  7. QTc Interval [ Time Frame: Baseline, cycle 1 day 15, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1, cycle 6 day 1, cycle 7 day 1, cycle 8 day 1, cycle 9 day 1 ]
    Time between the start of the Q wave and the end of the T wave corrected for heart rate

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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:

  1. Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
  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. No prior systemic anti-cancer therapy for advanced disease.
  4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
  5. 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.
  6. Patient must have either:

    • Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other locoregional therapy will only be considered measurable if disease progression at the treated site after completion of therapy is clearly documented).


    • If no measurable disease is present, then at least one predominantly lytic bone lesion must be present (Patients with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).

  7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

  1. Patient who received any CDK4/6 inhibitor.
  2. Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer


    • Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease free interval must be greater than 12 months from the completion of treatment until randomization.
    • Patients who received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization are eligible.
    • Any prior (neo) adjuvant anti-cancer therapy must be stopped at least 5 half-lives or 7 days, whichever is longer, before randomization
  3. Patient is concurrently using other anti-cancer therapy.
  4. 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.
  5. 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

    6. Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior start if the treatment:

  • 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.
  • Herbal preparations/medications

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): NCT01958021

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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: NCT01958021    
Other Study ID Numbers: CLEE011A2301
2013-003084-61 ( EudraCT Number )
First Posted: October 8, 2013    Key Record Dates
Results First Posted: May 12, 2017
Last Update Posted: April 26, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Advanced breast cancer
Phase III
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