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

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

ClinicalTrials.gov Identifier: NCT01958021

Novartis Reference Number: CLEE011A2301

See if you pre-qualify

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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

Condition 
Advanced, Metastatic Breast Cancer
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
668 participants
Start date 
Dec 17, 2013
Completion date 
Aug 31, 2022
Gender 
Female
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

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

Eligibility Criteria

Inclusion Criteria:

Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.

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.
No prior systemic anti-cancer therapy for advanced disease.
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 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.

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).

OR

• 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).

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

Exclusion Criteria:

Patient who received any CDK4/6 inhibitor.

Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer

Note:

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
Patient is concurrently using other anti-cancer therapy.
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.

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

Study Locations

United States
Ironwood Cancer and Research Centers SC
-
Chandler, 85224
Arizona
United States
Arizona Oncology Associates PC HAL
-
Sedona, 86336
Arizona
United States
Highlands Oncology Group
-
Fayetteville, 72703
Arkansas
United States
NEA Baptist Cancer Center
-
Jonesboro, 72401
Arkansas
United States
Alta Bates Cancer Center Oncology Dept.
-
Berkeley, 94704
California
United States
City of Hope National Medical Center SC-5
-
Duarte, 91010 3000
California
United States
Glendale-Adventist Medical Center Dept of Oncology
-
Glendale, 91206
California
United States
The Angeles Clinic and Research Institute SC-3
-
Los Angeles, 90025
California
United States
Cedars Sinai Medical Center SC-5
-
Los Angeles, 90048
California
United States
UC Davis Comprehensive Cancer Center SC-2
-
Sacramento, 95817
California
United States
University of Colorado School of Medicine Onc Dept.
-
Aurora, 80045
Colorado
United States
Rocky Mountain Cancer Centers RMCC - Aurora
-
Greenwood Village,
Colorado
United States
University Cancer Institute SC
-
Boynton Beach, 33426
Florida
United States
Florida Cancer Research Institute Dept of Oncology
-
Davie, 33328
Florida
United States
Florida Cancer Specialists FL Cancer Specialists
-
Fort Myers, 33901
Florida
United States
Memorial Hospital SC
-
Hollywood, 33021
Florida
United States
University of Miami Univ Miami 2
-
Miami, 33136
Florida
United States
Florida Retina Institute SC-3
-
Orlando, 32804
Florida
United States
Florida Retina Institute SC-5
-
Orlando, 32804
Florida
United States
Sacred Heart Medical Oncology SC
-
Pensacola, 32504
Florida
United States
Florida Cancer Specialists - North
-
Saint Petersburg, 33705
Florida
United States
Georgia Cancer Specialists Georgia Cancer Spec
-
Decatur, 30033
Georgia
United States
Lewis Hall Singletary Onc Ctr at John D. Archbold Mem Hosp. Onc Dept
-
Thomasville, 31792
Georgia
United States
Moanalua Medical Center. Attn: Oncology Dept
-
Honolulu, 96817
Hawaii
United States
University of Illinois Cancer Center at Chicago
-
Chicago, 60612
Illinois
United States
University of Chicago Dept. of Oncology
-
Chicago, 60637
Illinois
United States
North Shore University Health System
-
Evanston, 60201
Illinois
United States
Ingalls Memorial Hospital Ingalls Mem Hosp
-
Harvey, 60426
Illinois
United States
Edward Hospital Dept of Oncology
-
Naperville, 60540
Illinois
United States
Indiana University Simon Cancer Center
-
Indianapolis, 46202
Indiana
United States
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med SC-3
-
Baltimore, 21231
Maryland
United States
Frederick Memorial Hospital SC
-
Frederick, 21701
Maryland
United States
Dana Farber Cancer Institute Dana Farber-9
-
Boston, 02215
Massachusetts
United States
Virginia Piper Cancer Institute, Allina Health
-
Minneapolis, 55407
Minnesota
United States
Jackson Oncology Associates
-
Jackson, 39202
Mississippi
United States
Saint Luke's Hospital/Marion Bloch Neuroscience Institute Oncology Dept
-
Kansas City, 64111
Missouri
United States
Mercy Medical Research Institute SC-1
-
Manchester, 63021
Missouri
United States
Foundation Medical Partners
-
Nashua, 03060
New Hampshire
United States
Hackensack Meridian Health
-
Brick, 08724
New Jersey
United States
Cooper Cancer Center Cooper Cancer Center
-
Camden, 08103
New Jersey
United States
Cancer Institute of New Jersey Onc Dept
-
New Brunswick, 08901
New Jersey
United States
Montefiore Medical Center SC-8
-
Bronx, 10467
New York
United States
CR Wood Cancer Center
-
Glens Falls, 12801
New York
United States
Winthrop University Hospital Onc Dept
-
Mineola, 11501
New York
United States
NYU Langone Medical Center CV Research center SC-2
-
New York, 10016
New York
United States
Mount Sinai School of Medicine SC
-
New York, 10029
New York
United States
Duke University Medical Center SC-8
-
Durham, 27710
North Carolina
United States
Oncology Hematology Care Inc Oncology Hematology Care (3)
-
Cincinnati, 45242
Ohio
United States
The Ohio State University Comprehensive Cancer Center Ohio State-2
-
Columbus, 43221
Ohio
United States
Mercy Clinic Oklahoma Communities Mercy Oncology
-
Oklahoma City, 73120
Oklahoma
United States
Lehigh Valley Hospital Onc Dept
-
Allentown, 18103
Pennsylvania
United States
Penn State University Milton S Hershey Medical Center SC-3
-
Hershey, 17033
Pennsylvania
United States
Avera Cancer SC-2
-
Sioux Falls, 57105
South Dakota
United States
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
-
Chattanooga, 37404
Tennessee
United States
Sarah Cannon Research Institute SC-2
-
Nashville, 37203
Tennessee
United States
Vanderbilt University Medical Center SC-4
-
Nashville, 37232
Tennessee
United States
Texas Oncology, P.A.
-
Bedford, 76022
Texas
United States
Texas Oncology P A SC-3
-
Dallas, 75251
Texas
United States
University of Texas Southwestern Medical Center
-
Dallas, 75390
Texas
United States
Center for Cancer and Blood Disorders SC
-
Fort Worth, 76104
Texas
United States
Texas Oncology, P.A.
-
Fort Worth, 76104
Texas
United States
Texas Oncology Houston Memorial City SC
-
Houston, 77024
Texas
United States
University of Texas MD Anderson Cancer Center UT MDAnderson
-
Houston, 77030
Texas
United States
Millennium Oncology SC
-
Houston, 77090
Texas
United States
Texas Oncology
-
McAllen, 78503
Texas
United States
Richardson Hematology Oncology Associates
-
Richardson, 75082
Texas
United States
Texas Oncology P A
-
San Antonio, 78217
Texas
United States
US Oncology P A
-
Tyler, 75702
Texas
United States
Utah Cancer Specialists Utah Cancer Specialists (11)
-
Salt Lake City, 84106
Utah
United States
Virginia Cancer Specialists Fairfax Northern Virginia
-
Fairfax, 22031
Virginia
United States
Oncology and Hematology Associates of Southwest Virginia Inc
-
Salem, 24153
Virginia
United States
Providence Regional Cancer Partnership
-
Everett, 98201
Washington
United States
Northwest Medical Specialties Dept of Onc
-
Tacoma, 98405
Washington
United States
Dean Health System Onc Dept
-
Madison, 53717
Wisconsin
United States
Argentina
Novartis Investigative Site
-
San Miguel De Tucuman, T4000IAK
Tucuman
Argentina
Novartis Investigative Site
-
Cordoba, X5002AOQ
-
Argentina
Novartis Investigative Site
-
La Rioja, 5300
-
Argentina
Australia
Novartis Investigative Site
-
Kurralta Park, 5037
South Australia
Australia
Novartis Investigative Site
-
East Melbourne, 3002
Victoria
Australia
Novartis Investigative Site
-
Nedlands, 6009
Western Australia
Australia
Austria
Novartis Investigative Site
-
Salzburg, 5020
-
Austria
Novartis Investigative Site
-
Vienna, A-1100
-
Austria
Novartis Investigative Site
-
Wien, A-1090
-
Austria
Belgium
Novartis Investigative Site
-
Sint Niklaas, 9100
Vlaams Brabant
Belgium
Novartis Investigative Site
-
Hasselt, 3500
-
Belgium
Novartis Investigative Site
-
Leuven, 3000
-
Belgium
Novartis Investigative Site
-
Namur, 5000
-
Belgium
Novartis Investigative Site
-
Wilrijk, 2610
-
Belgium
Brazil
Novartis Investigative Site
-
Ribeirao Preto, 14048-900
SP
Brazil
Novartis Investigative Site
-
Sao Paulo, 01246 000
SP
Brazil
Novartis Investigative Site
-
Sao Paulo, 01317-002
SP
Brazil
Canada
Novartis Investigative Site
-
Burnaby, V5G 2X6
British Columbia
Canada
Novartis Investigative Site
-
Halifax, B3H 1V7
Nova Scotia
Canada
Novartis Investigative Site
-
Hamilton, L8V 5C2
Ontario
Canada
Novartis Investigative Site
-
Kitchener, N2G 1G3
Ontario
Canada
Novartis Investigative Site
-
Ottawa, K1H 8L6
Ontario
Canada
Novartis Investigative Site
-
Toronto, M4N 3M5
Ontario
Canada
Novartis Investigative Site
-
Montreal, H2W 1T8
Quebec
Canada
Novartis Investigative Site
-
Quebec, G1S 4L8
-
Canada
Czechia
Novartis Investigative Site
-
Brno Bohunice, 625 00
Czech Republic
Czechia
Novartis Investigative Site
-
Brno, 656 53
Czech Republic
Czechia
Novartis Investigative Site
-
Liberec, 46063
Czech Republic
Czechia
Novartis Investigative Site
-
Olomouc, 775 20
CZE
Czechia
Denmark
Novartis Investigative Site
-
Aarhus, DK-8000
-
Denmark
Novartis Investigative Site
-
Copenhagen, DK-2100
-
Denmark
Novartis Investigative Site
-
Odense C, DK 5000
-
Denmark
Novartis Investigative Site
-
Vejle, 7100
-
Denmark
Finland
Novartis Investigative Site
-
Helsinki, 00029
-
Finland
Novartis Investigative Site
-
Turku, FIN-20520
-
Finland
France
Novartis Investigative Site
-
Nice Cedex 2, 06189
Alpes Maritimes
France
Novartis Investigative Site
-
France, 94800
Villejuif
France
Novartis Investigative Site
-
Angers Cedex 02, 49055
-
France
Novartis Investigative Site
-
Avignon Cedex, 84082
-
France
Novartis Investigative Site
-
Besancon Cedex, 25030
-
France
Novartis Investigative Site
-
Bordeaux Cedex, 33000
-
France
Novartis Investigative Site
-
Creteil, 94000
-
France
Novartis Investigative Site
-
Le Mans Cedex, 72015
-
France
Novartis Investigative Site
-
Lyon Cedex, 69373
-
France
Novartis Investigative Site
-
Pierre Benite Cedex, 69495
-
France
Novartis Investigative Site
-
Rouen Cedex 1, 76038
-
France
Novartis Investigative Site
-
Saint-Herblain Cédex, 44805
-
France
Germany
Novartis Investigative Site
-
Recklinghausen, 45657
North Rhine-westphalia
Germany
Novartis Investigative Site
-
Aschaffenburg, 63739
-
Germany
Novartis Investigative Site
-
Berlin, 14169
-
Germany
Novartis Investigative Site
-
Berlin, 14195
-
Germany
Novartis Investigative Site
-
Bielefeld, 33604
-
Germany
Novartis Investigative Site
-
Bonn, 53111
-
Germany
Novartis Investigative Site
-
Bottrop, 46236
-
Germany
Novartis Investigative Site
-
Duesseldorf, 40225
-
Germany
Novartis Investigative Site
-
Erlangen, 91054
-
Germany
Novartis Investigative Site
-
Essen, 45136
-
Germany
Novartis Investigative Site
-
Freiburg, 79110
-
Germany
Novartis Investigative Site
-
Fuerth, 90766
-
Germany
Novartis Investigative Site
-
Goslar, 38642
-
Germany
Novartis Investigative Site
-
Heidelberg, 69120
-
Germany
Novartis Investigative Site
-
Muenchen, 80335
-
Germany
Novartis Investigative Site
-
Offenbach, 63069
-
Germany
Novartis Investigative Site
-
Ravensburg, 88214
-
Germany
Novartis Investigative Site
-
Tübingen, 72076
-
Germany
Novartis Investigative Site
-
Ulm, 89081
-
Germany
Novartis Investigative Site
-
Velbert, 42551
-
Germany
Hungary
Novartis Investigative Site
-
Budapest, 1134
-
Hungary
Novartis Investigative Site
-
Debrecen, 4032
-
Hungary
Novartis Investigative Site
-
Gyor, H-9023
-
Hungary
Novartis Investigative Site
-
Gyula, 5700
-
Hungary
Ireland
Novartis Investigative Site
-
Cork,
-
Ireland
Novartis Investigative Site
-
Dublin 4, 4
-
Ireland
Israel
Novartis Investigative Site
-
Petach Tikva, 49100
-
Israel
Novartis Investigative Site
-
Ramat Gan, 52621
-
Israel
Novartis Investigative Site
-
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
-
Brescia, 25123
BS
Italy
Novartis Investigative Site
-
Genova, 16132
GE
Italy
Novartis Investigative Site
-
Lecco, 23900
LC
Italy
Novartis Investigative Site
-
Macerata, 62100
MC
Italy
Novartis Investigative Site
-
Messina, 98158
ME
Italy
Novartis Investigative Site
-
Milano, 20133
MI
Italy
Novartis Investigative Site
-
Padova, 35100
PD
Italy
Novartis Investigative Site
-
Perugia, 06129
PG
Italy
Novartis Investigative Site
-
Pisa, 56126
PI
Italy
Novartis Investigative Site
-
Aviano, 33081
PN
Italy
Novartis Investigative Site
-
Reggio Calabria, 89124
RC
Italy
Novartis Investigative Site
-
Roma, 00168
RM
Italy
Novartis Investigative Site
-
Candiolo, 10060
TO
Italy
Novartis Investigative Site
-
Terni, 05100
TR
Italy
Novartis Investigative Site
-
Viterbo, 01100
VT
Italy
Novartis Investigative Site
-
Napoli, 80131
-
Italy
Korea, Republic of
Novartis Investigative Site
-
Bundang Gu, 13620
Gyeonggi Do
Korea, Republic of
Novartis Investigative Site
-
Gyeonggi do, 10408
Korea
Korea, Republic of
Novartis Investigative Site
-
Seoul, 05505
Korea
Korea, Republic of
Novartis Investigative Site
-
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
-
Seoul, 03722
-
Korea, Republic of
Lebanon
Novartis Investigative Site
-
Ashrafieh, 166830
-
Lebanon
Novartis Investigative Site
-
Beirut, 1107 2020
-
Lebanon
Novartis Investigative Site
-
Beirut,
-
Lebanon
Novartis Investigative Site
-
Saida, 652
-
Lebanon
Netherlands
Novartis Investigative Site
-
Maastricht, 5800
AZ
Netherlands
Novartis Investigative Site
-
Alkmaar, 1815 JD
-
Netherlands
Novartis Investigative Site
-
Amsterdam, 1066 CX
-
Netherlands
Novartis Investigative Site
-
Deventer, 7416 SE
-
Netherlands
Novartis Investigative Site
-
Groningen, 9713 GZ
-
Netherlands
Novartis Investigative Site
-
Groningen, 9728 NZ
-
Netherlands
Novartis Investigative Site
-
Leiden, 2300 RC
-
Netherlands
Novartis Investigative Site
-
Sittard-Geleen, 6162 BG
-
Netherlands
Novartis Investigative Site
-
Tilburg, 5042 AD
-
Netherlands
Novartis Investigative Site
-
Zwolle, 8025 AB
-
Netherlands
Norway
Novartis Investigative Site
-
Bergen, 5021
-
Norway
Novartis Investigative Site
-
Oslo, 0407
-
Norway
Russian Federation
Novartis Investigative Site
-
Arkhangelsk, 163045
-
Russian Federation
Novartis Investigative Site
-
Nizhniy Novgorod,
-
Russian Federation
Novartis Investigative Site
-
Ryazan, 390011
-
Russian Federation
Singapore
Novartis Investigative Site
-
Singapore, 169610
-
Singapore
South Africa
Novartis Investigative Site
-
Pretoria, 0081
Gauteng
South Africa
Spain
Novartis Investigative Site
-
Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
-
Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
-
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
-
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
-
Barcelona, 08024
Cataluña
Spain
Novartis Investigative Site
-
Valencia, 46009
Comunidad Valenciana
Spain
Novartis Investigative Site
-
Santiago de Compostela, 15706
Galicia
Spain
Novartis Investigative Site
-
La Laguna, 38320
Santa Cruz De Tenerife
Spain
Novartis Investigative Site
-
Madrid, 28009
-
Spain
Novartis Investigative Site
-
Madrid, 28040
-
Spain
Novartis Investigative Site
-
Madrid, 28041
-
Spain
Novartis Investigative Site
-
Madrid, 28046
-
Spain
Sweden
Novartis Investigative Site
-
Eskilstuna, SE-631 88
-
Sweden
Novartis Investigative Site
-
Goteborg, 413 45
-
Sweden
Novartis Investigative Site
-
Joenkoeping, 551 85
-
Sweden
Novartis Investigative Site
-
Lund, 221 85
-
Sweden
Novartis Investigative Site
-
Uppsala, SE-751 85
-
Sweden
Novartis Investigative Site
-
Vaxjo, SE-351 85
-
Sweden
Taiwan
Novartis Investigative Site
-
Kuei-Shan Chiang, 33305
Taoyuan/ Taiwan ROC
Taiwan
Novartis Investigative Site
-
New Taipei City, 23561
TWN
Taiwan
Novartis Investigative Site
-
Kaohsiung, 80756
-
Taiwan
Novartis Investigative Site
-
Taipei, 10048
-
Taiwan
Novartis Investigative Site
-
Taipei, 11217
-
Taiwan
Thailand
Novartis Investigative Site
-
Bangkok, 10330
-
Thailand
Turkey
Novartis Investigative Site
-
Ankara, 06100
-
Turkey
Novartis Investigative Site
-
Ankara, 06590
-
Turkey
Novartis Investigative Site
-
Diyarbakir, 21000
-
Turkey
Novartis Investigative Site
-
Istanbul, 34303
-
Turkey
Novartis Investigative Site
-
Izmir, 35040
-
Turkey
United Kingdom
Novartis Investigative Site
-
Truro, TR1 3LJ
Cornwall
United Kingdom
Novartis Investigative Site
-
Newcastle upon Tyne, NE7 7DN
-
United Kingdom

Have a question?

Call 1-999-669-6682 or email [email protected]