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Advanced, Metastatic Breast CancerPhase 3MONALEESA-2NCT01958021

Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer

A Phase 3 study testing Ribociclib and Letrozole in people with Advanced, Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 221 sites in 29 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary purpose of this study was to assess the efficacy of ribociclib, as measured by progression free survival (PFS), in postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who received no prior treatment for advanced disease. Read more about this study

Who is it for?
Ages 18 to 100 years, women only
Conditions the study is for
Advanced, Metastatic Breast Cancer
What is being tested?
Ribociclib and Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
668 participants
Where
221 sitesin 29 countries
Study dates
17 Dec 2013to 16 Mar 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women with advanced (locoregionally recurrent or metastatic) breast cancer that was not amenable to curative therapy.
  • The patient was postmenopausal. Postmenopausal status was 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.
  • There was no prior systemic anti-cancer therapy for advanced disease.
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  • The patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by the local laboratory.
  • The patient had HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC was 2+, a negative in situ hybridization (FISH, CISH, or SISH) test was required by local laboratory testing.
  • The patient must have had 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 were considered measurable if disease progression at the treated site after completion of therapy was clearly documented). OR If no measurable disease was present, then at least one predominantly lytic bone lesion must have been present (Patients with no measurable disease and only one predominantly lytic bone lesion previously irradiated were eligible if there was documented evidence of disease progression of the bone lesion after irradiation).
  • The patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Who cannot join

  • The patient had received any CDK4/6 inhibitor.
  • The patient had received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer.
  • Note:
  • Patients who had received (neo) adjuvant therapy for breast cancer were eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole, the disease-free interval had to be greater than 12 months from the completion of treatment until randomization.
  • Patients who had received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization were eligible.
  • Any prior (neo) adjuvant anti-cancer therapy had to be stopped at least 5 half-lives or 7 days, whichever was longer, before randomization.
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  • The patient was concurrently using other anti-cancer therapy.
  • The patient had 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.
  • The patient had 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.
  • The patient had 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.
  • The patient was currently receiving any of the following medications and could not be discontinued 7 days prior to the start of treatment:
  • Medications known to be strong inducers or inhibitors of CYP3A4.
  • Medications known to have a risk of prolonging the QT interval or inducing Torsades de Pointes.
  • Medications with a narrow therapeutic window and predominantly metabolized through CYP3A4.
  • Herbal preparations/medications.

Trial locations and contacts

221 sites in 29 countries.

221 sites in 29 countries

United States73 sites

  • Lehigh Valley Hospital

    Allentown, Pennsylvania, 18103

  • Univ of Colorado School of Medicine

    Aurora, Colorado, 80045

  • Sidney Kimmel CCC At JH

    Baltimore, Maryland, 21231

  • Texas Oncology P A

    Bedford, Texas, 76022

  • Alta Bates Cancer Center

    Berkeley, California, 94704

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University Cancer Institute

    Boynton Beach, Florida, 33426

  • Cooper Cancer Center

    Camden, New Jersey, 08103

  • Ironwood Cancer and Research Centers

    Chandler, Arizona, 85224

  • Chattanooga Onc And Hem Assoc PC

    Chattanooga, Tennessee, 37404

  • University of Illinois Cancer Center at Chicago

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637

  • Oncology Hematology Care Inc

    Cincinnati, Ohio, 45242

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43221

  • Texas Oncology

    Dallas, Texas, 75251

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Florida Cancer Research Institute

    Davie, Florida, 33328

  • Georgia Cancer Specialists

    Decatur, Georgia, 30033

  • City of Hope National Medical Center

    Duarte, California, 91010 3000

  • Duke Univ Medical Center

    Durham, North Carolina, 27710

  • Hackensack Meridian Health

    Edison, New Jersey, 88837

  • NorthShore University Health System

    Evanston, Illinois, 60201

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • Ctr For Cancer And Blood Disorders

    Fort Worth, Texas, 76104

  • Texas Oncology P A

    Fort Worth, Texas, 76104

  • Frederick Memorial Hospital

    Frederick, Maryland, 21701

  • Glendale Adventist Medical Center

    Glendale, California, 91206

  • C R Wood Cancer Center at Glens Falls Hospital

    Glens Falls, New York, 12801

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Penn State Hershey Cancer Institute

    Hershey, Pennsylvania, 17033

  • Memorial Hospital

    Hollywood, Florida, 33021

  • Moanalua Medical Center Attn Oncology Dept

    Honolulu, Hawaii, 96817

  • Texas Oncology Houston Memorial City

    Houston, Texas, 77024

  • Uni Of TX MD Anderson Cancer Cntr

    Houston, Texas, 77030

  • Millennium Research Clin Develop

    Houston, Texas, 77090

  • IU Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Jackson Oncology Associates

    Jackson, Mississippi, 39202

  • NEA Baptist Cancer Center

    Jonesboro, Arkansas, 72401

  • St Lukes Hos Marion Bloch Neur Inst

    Kansas City, Missouri, 64111

  • Rocky Mountain Cancer Centers

    Longmont, Colorado, 80501

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Cedars Sinai Medical Center SC-5

    Los Angeles, California, 90048

  • Dean Health System

    Madison, Wisconsin, 53717

  • Mercy Medical Research Institute

    Manchester, Missouri, 63021

  • Texas Oncology

    McAllen, Texas, 78503

  • University Of Miami

    Miami, Florida, 33136

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Allina Hlth Cancer Inst Minneapolis

    Minneapolis, Minnesota, 55407

  • Edward Hospital

    Naperville, Illinois, 60540

  • Foundation Medical Partners

    Nashua, New Hampshire, 03060

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Ctr

    Nashville, Tennessee, 37232

  • Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • NYU Langone Med Center CV Research

    New York, New York, 10016

  • Mount Sinai School Of Medicine

    New York, New York, 10029

  • Mercy Clinic Oklahoma Communities Mercy Oncology

    Oklahoma City, Oklahoma, 73120

  • Florida Retina Institute

    Orlando, Florida, 32804

  • Sacred Heart Medical Oncology

    Pensacola, Florida, 32504

  • Richardson Hematology Oncology Associates

    Richardson, Texas, 75082

  • Comprehensive Cancer Center

    Sacramento, California, 95817

  • Oncology and Hematology Associates of Southwest Virginia Inc

    Salem, Virginia, 24153

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • Texas Oncology P A

    San Antonio, Texas, 78217

  • Arizona Oncology Associates PC HAL

    Sedona, Arizona, 86336

  • Avera Cancer

    Sioux Falls, South Dakota, 57105

  • Florida Cancer Specialists-North

    St. Petersburg, Florida, 33705

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Lewis Hall Singletary Onc Ctr at John D. Archbold Mem Hosp.

    Thomasville, Georgia, 31792

  • Texas Oncology Northeast Texas

    Tyler, Texas, 75702

Other trials in United States

Germany20 sites

  • Novartis Investigative Site

    Aschaffenburg, 63739

  • Novartis Investigative Site

    Berlin, 14169

  • Novartis Investigative Site

    Berlin, 14195

  • Novartis Investigative Site

    Bielefeld, North Rhine-Westphalia, 33604

  • Novartis Investigative Site

    Bonn, 53111

  • Novartis Investigative Site

    Bottrop, 46236

  • Novartis Investigative Site

    Düsseldorf, 40225

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Essen, 45136

  • Novartis Investigative Site

    Freiburg im Breisgau, 79110

  • Novartis Investigative Site

    Fürth, 90766

  • Novartis Investigative Site

    Goslar, 38642

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    München, 80335

  • Novartis Investigative Site

    Offenbach, 63069

  • Novartis Investigative Site

    Ravensburg, 88214

  • Novartis Investigative Site

    Recklinghausen, 45657

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Ulm, 89081

  • Novartis Investigative Site

    Velbert, 42551

Other trials in Germany

Italy15 sites

  • Novartis Investigative Site

    Aviano, PN, 33081

  • Novartis Investigative Site

    Brescia, BS, 25123

  • Novartis Investigative Site

    Candiolo, TO, 10060

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Lecco, LC, 23900

  • Novartis Investigative Site

    Messina, ME, 98158

  • Novartis Investigative Site

    Milan, MI, 20133

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Padova, PD, 35100

  • Novartis Investigative Site

    Perugia, PG, 06129

  • Novartis Investigative Site

    Pisa, PI, 56124

  • Novartis Investigative Site

    Reggio Calabria, RC, 89100

  • Novartis Investigative Site

    Roma, RM, 00168

  • Novartis Investigative Site

    Terni, TR, 05100

  • Novartis Investigative Site

    Viterbo, VT, 01100

Other trials in Italy

France12 sites

  • Novartis Investigative Site

    Angers, 49055

  • Novartis Investigative Site

    Avignon, 84082

  • Novartis Investigative Site

    Besançon, 25030

  • Novartis Investigative Site

    Bordeaux, 33000

  • Novartis Investigative Site

    Créteil, 94000

  • Novartis Investigative Site

    Le Mans, 72000

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Nice, Alpes Maritimes, 06189

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Rouen, 76038

  • Novartis Investigative Site

    Saint-Herblain, 44805

  • Novartis Investigative Site

    Villejuif, 94800

Other trials in France

Spain12 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08024

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Catalonia, 08907

  • Novartis Investigative Site

    Madrid, 28009

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Madrid, 28046

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

  • Novartis Investigative Site

    San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320

  • Novartis Investigative Site

    Santiago de Compostela, Galicia, 15706

  • Novartis Investigative Site

    Seville, Andalusia, 41013

  • Novartis Investigative Site

    Valencia, Valencia, 46009

Other trials in Spain

Netherlands10 sites

  • Novartis Investigative Site

    Alkmaar, 1815 JD

  • Novartis Investigative Site

    Deventer, 7416 SE

  • Novartis Investigative Site

    Groningen, 9713 GZ

  • Novartis Investigative Site

    Groningen, 9728 NZ

  • Novartis Investigative Site

    Leiden, South Holland, 2333 ZA

  • Novartis Investigative Site

    Maastricht, 6229 HX

  • Novartis Investigative Site

    Sittard-Geleen, BG, 6162 BG

  • Novartis Investigative Site

    Tilburg, 5042 AD

  • Novartis Investigative Site

    Zoetermeer, NL-2722 EP

  • Novartis Investigative Site

    Zwolle, 8025 AB

Other trials in Netherlands

Canada8 sites

  • Novartis Investigative Site

    Burnaby, British Columbia, V5G 2X6

  • Novartis Investigative Site

    Halifax, Nova Scotia, B3H 2Y9

  • Novartis Investigative Site

    Hamilton, Ontario, L8V 5C2

  • Novartis Investigative Site

    Kitchener, Ontario, N2G 1G3

  • Novartis Investigative Site

    Montreal, Quebec, H2X 0A9

  • Novartis Investigative Site

    Ottawa, Ontario, K1H 8L6

  • Novartis Investigative Site

    Québec, Quebec, G1S 4L8

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Sweden6 sites

  • Novartis Investigative Site

    Eskilstuna, SE-631 88

  • Novartis Investigative Site

    Gothenburg, 413 45

  • Novartis Investigative Site

    Jönköping, 551 85

  • Novartis Investigative Site

    Lund, 221 85

  • Novartis Investigative Site

    Uppsala, 751 85

  • Novartis Investigative Site

    Vaxjo, SE-351 85

Other trials in Sweden

Belgium5 sites

  • Novartis Investigative Site

    Hasselt, 3500

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Namur, 5000

  • Novartis Investigative Site

    Sint-Niklaas, Oost Vlaanderen, 9100

  • Novartis Investigative Site

    Wilrijk, 2610

Other trials in Belgium

South Korea5 sites

  • Novartis Investigative Site

    Bundang Gu, Gyeonggi-do, 13620

  • Novartis Investigative Site

    Gyeonggi-do, Korea, 10408

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 03722

  • Novartis Investigative Site

    Seoul, 05505

Other trials in South Korea

Taiwan5 sites

  • Novartis Investigative Site

    Kaohsiung City, 80756

  • Novartis Investigative Site

    New Taipei City, 23561

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taipei, 11217

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Turkey (Türkiye)5 sites

  • Novartis Investigative Site

    Ankara, 06230

  • Novartis Investigative Site

    Ankara, 06590

  • Novartis Investigative Site

    Diyarbakır, 21000

  • Novartis Investigative Site

    Istanbul, 35100

  • Novartis Investigative Site

    Izmir, 35100

Other trials in Turkey (Türkiye)

Czechia4 sites

  • Novartis Investigative Site

    Brno, Czech Republic, 656 53

  • Novartis Investigative Site

    Brno-Bohunice, 625 00

  • Novartis Investigative Site

    Liberec, 46063

  • Novartis Investigative Site

    Olomouc, 779 00

Other trials in Czechia

Denmark4 sites

  • Novartis Investigative Site

    Aarhus, DK-8000

  • Novartis Investigative Site

    Copenhagen, DK-2100

  • Novartis Investigative Site

    Odense C, DK 5000

  • Novartis Investigative Site

    Vejle, 7100

Other trials in Denmark

Hungary4 sites

  • Novartis Investigative Site

    Budapest, Pest County, 1134

  • Novartis Investigative Site

    Debrecen, 4032

  • Novartis Investigative Site

    Győr, H-9024

  • Novartis Investigative Site

    Gyula, 5700

Other trials in Hungary

Lebanon4 sites

  • Novartis Investigative Site

    Beirut, 10999

  • Novartis Investigative Site

    Beirut, 1107 2020

  • Novartis Investigative Site

    El Achrafiyé, 166830

  • Novartis Investigative Site

    Saida, 652

Other trials in Lebanon

Argentina3 sites

  • Novartis Investigative Site

    Córdoba, X5002AOQ

  • Novartis Investigative Site

    La Rioja, 5300

  • Novartis Investigative Site

    San Miguel de Tucumán, Tucumán Province, T4000IAK

Other trials in Argentina

Australia3 sites

  • Novartis Investigative Site

    East Melbourne, Victoria, 3002

  • Novartis Investigative Site

    Kurralta Park, South Australia, 5037

  • Novartis Investigative Site

    Nedlands, Western Australia, 6009

Other trials in Australia

Austria3 sites

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, A-1090

  • Novartis Investigative Site

    Vienna, A-1100

Other trials in Austria

Brazil3 sites

  • Novartis Investigative Site

    Ribeirão Preto, São Paulo, 14048-900

  • Novartis Investigative Site

    São Paulo, São Paulo, 01246 000

  • Novartis Investigative Site

    São Paulo, São Paulo, 01317-002

Other trials in Brazil

Israel3 sites

  • Novartis Investigative Site

    Petah Tikva, 4941492

  • Novartis Investigative Site

    Ramat Gan, 52621

  • Novartis Investigative Site

    Tel Aviv, 6423906

Other trials in Israel

Russia3 sites

  • Novartis Investigative Site

    Arkhangelsk, 163045

  • Novartis Investigative Site

    Nizhny Novgorod, 603000

  • Novartis Investigative Site

    Ryazan, 390011

Other trials in Russia

Finland2 sites

  • Novartis Investigative Site

    Helsinki, 00029

  • Novartis Investigative Site

    Turku, FIN-20520

Other trials in Finland

Ireland2 sites

  • Novartis Investigative Site

    Cork, 190384

  • Novartis Investigative Site

    Dublin, DO4

Other trials in Ireland

Norway2 sites

  • Novartis Investigative Site

    Bergen, NO-5021

  • Novartis Investigative Site

    Oslo, NO-0407

Other trials in Norway

United Kingdom2 sites

  • Novartis Investigative Site

    Newcastle upon Tyne, NE7 7DN

  • Novartis Investigative Site

    Truro, Cornwall, TR1 3LJ

Other trials in United Kingdom

Singapore1 site

  • Novartis Investigative Site

    Singapore, 168583

Other trials in Singapore

South Africa1 site

  • Novartis Investigative Site

    Pretoria, Gauteng, 0081

Other trials in South Africa

Thailand1 site

  • Novartis Investigative Site

    Bangkok, 10330

Other trials in Thailand

About this study

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

The primary purpose of this study was to assess the efficacy of ribociclib, as measured by progression free survival (PFS), in postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who received no prior treatment for advanced disease.

Read the detailed description

This was an international, multi-center, randomized, double-blinded, placebo controlled Phase III trial to determine the efficacy and safety of treatment with ribociclib plus letrozole versus placebo plus letrozole in postmenopausal women with HR+, HER2-negative advanced breast cancer who received no prior therapy for advanced disease.

Eligible patients were randomized in 1:1 ratio to either ribociclib group or placebo group. Study treatment continued until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Participants who discontinued treatment due to reasons other than disease progression or withdrawal of consent for efficacy follow-up continued to be monitored until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy follow-up).

All participants who discontinued treatment were followed for survival until the predetermined number of overall survival (OS) events was reached.

Following the final OS analysis (performed when approximately 400 deaths were recorded) and with protocol amendment 10 (dated 30-Apr-2021), participants and investigators were unblinded and those participants in the placebo arm had the opportunity to cross-over to the ribociclib arm to receive ribociclib plus letrozole. Cross-over was optional and was conducted at the investigator's discretion and upon participant consent.

Being tested
Ribociclib, Letrozole, Placebo
Keywords
HR-positive, HER2-negative, Advanced breast cancer, LEE011, Letrozole, CDK, CDK4, CDK6, CDK4/6, Phase III, ER-positive, PR-positive, Postmenopausal
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RibociclibDrug

    Also called LEE011

    Ribociclib (600 mg, in three 200 mg hard gelatin capsules or tablets) was administered orally once daily on Days 1-21 of each 28-day cycle.

  • LetrozoleDrug

    Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle)

  • PlaceboDrug

    Placebo (hard gelatin capsules or tablets) was administered orally once daily on Days 1-21 of each 28-day cycle.

Study groups in NCT01958021
Study groupRoleWhat they receive
Ribociclib+ letrozoleExperimentalRibociclib 600 mg daily oral (3 weeks on/ 1 week off) in combination with letrozole 2.5 mg daily oral
Receives: Drug: Ribociclib; Drug: Letrozole
Placebo + letrozolePlacebo comparatorPlacebo daily oral (3 weeks on/ 1 week off) in combination with letrozole 2.5 mg daily oral. Participants were unblinded once the final OS analysis was completed and after the implementation of protocol amendment 10 (30-Apr-21) and were given the option to crossover to treatment with ribociclib + letrozole
Receives: Drug: Letrozole; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) by Investigator Assessment

    PFS was defined as the period starting from the date of randomization to the date of the first documented progression or death caused by any reason. In cases where patients did not experience an event, the PFS was censored at the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression.PFS was assessed by investigator assessment according to RECIST 1.1. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported for each treatment group. A stratified Cox regression model was used to estimate the hazard ratio of PFS, along with 95% confidence interval

    Measured: Up to 23 months

Secondary outcomes (6)

  1. Overall Survival (OS)

    OS was defined as the time from the date of randomization to the date of death from any cause. In cases where the patient's death was not recorded, the OS value was censored at the date of the last known patient's survival status.OS was estimated using the Kaplan-Meier method. As per protocol, the final OS analysis was conducted after approximately 400 deaths were documented.

    The median OS, along with 95% confidence intervals, was reported for each treatment group.The distribution of OS between the two treatment arms was compared using a log-rank test at one-sided cumulative 2.5% level of significance. A stratified Cox regression was used to estimate the OS hazard ratio and the associated 95% CI.

    Measured: Up to approximately 87 months

  2. Overall Response Rate (ORR) by Investigator Assessment

    ORR is the percentage of participants with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 as per investigator assessment. . 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.

    Measured: Up to 23 months

  3. Clinical Benefit Rate (CBR) by Investigator Assessment

    Percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1 as per investigator assessment. 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; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease: PD = At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20% the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Up to 23 months

  4. Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score

    ECOG PS categorized patients based on their ability to perform daily activities and self-care, with scores ranging from 0 to 5. A score of 0 indicated no restrictions in activity, while higher scores indicated increasing limitations. Time to definitive deterioration was defined as the time from the date of randomization to the date of the event, defined as experiencing an increase in ECOG PS by at least one category from the baseline or death. A deterioration was considered definitive if no improvements in the ECOG PS were observed at a subsequent time. The Kaplan-Meier method was used to estimate the distribution, and the median time to definitive deterioration, along with 95% confidence intervals, was reported for each treatment group. Patients receiving any further therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Patients that had not worsened at the data cutoff point were censored at the date of last assessment.

    Measured: From baseline up to 23 months

  5. Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)

    The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.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 QoL score (without further improvement above the threshold) or death due to any cause. The Kaplan-Meier method was used to estimate the distribution, and the median time to definitive 10% deterioration, along with 95% confidence intervals, was reported for each treatment group. If a patient had not had an event, time to deterioration was censored at the date of the last adequate QoL evaluation.

    Measured: From baseline up to 23 months

  6. Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30

    The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The change from baseline in the GHS/QoL score was assesed. A positive change from baseline indicated improvement.

    For subjects who discontinued treatment earlier and without disease progression, post-treatment efficacy follow-up visits occurred every 8 weeks after End of treatment (EOT) during the initial 18 months since start of treatment, followed by visits every 12 weeks until disease progression or end of study.

    Measured: Baseline, every 2 cycles for 18 months, then every 3 cycles until last dose; at EOT (within 15 days from last dose);every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to 23 months. Cycle=28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2013 (estimated)
  2. Study start17 Dec 2013
  3. Primary completion29 Jan 2016
  4. Study completion16 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
668 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01958021
Sponsor's protocol ID
CLEE011A2301
Other IDs
2013-003084-61
Acronym
MONALEESA-2
Status last verified
Feb 2025
First submitted
4 Oct 2013
Last updated
7 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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 www.clinicalstudydatarequest.com.

Publications

  • Ji Y, Wang C, Combes FP, Ho YY, Fasching PA, Untch M, Zarate JP, Crown J. Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer. Clin Pharmacokinet. 2026 Aug;65(8):1217-1228. doi: 10.1007/s40262-026-01643-3. Epub 2026 Jun 23.

    PubMed 42334791

  • Jhaveri K, O'Shaughnessy J, Fasching PA, Tolaney SM, Yardley DA, Sharma VK, Biswas C, Thuerigen A, Pathak P, Rugo HS. Matching-adjusted indirect comparison of PFS and OS comparing ribociclib plus letrozole versus palbociclib plus letrozole as first-line treatment of HR+/HER2- advanced breast cancer. Ther Adv Med Oncol. 2023 Dec 14;15:17588359231216095. doi: 10.1177/17588359231216095. eCollection 2023.

    PubMed 38107828

  • Andre F, Su F, Solovieff N, Hortobagyi G, Chia S, Neven P, Bardia A, Tripathy D, Lu YS, Lteif A, Taran T, Babbar N, Slamon D, Arteaga CL. Pooled ctDNA analysis of MONALEESA phase III advanced breast cancer trials. Ann Oncol. 2023 Nov;34(11):1003-1014. doi: 10.1016/j.annonc.2023.08.011. Epub 2023 Sep 5.

    PubMed 37673211

  • Rugo HS, Harmer V, O'Shaughnessy J, Jhaveri K, Tolaney SM, Cardoso F, Bardia A, Maheshwari VK, Tripathi S, Haftchenary S, Pathak P, Fasching PA. Quality of life with ribociclib versus abemaciclib as first-line treatment of HR+/HER2- advanced breast cancer: a matching-adjusted indirect comparison. Ther Adv Med Oncol. 2023 Feb 24;15:17588359231152843. doi: 10.1177/17588359231152843. eCollection 2023.

    PubMed 36861085

  • Ji Y, Yartsev V, Quinlan M, Serra P, Wang Y, Chakraborty A, Miller M. Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials. Clin Pharmacokinet. 2023 Mar;62(3):493-504. doi: 10.1007/s40262-022-01206-2. Epub 2023 Feb 17.

    PubMed 36800111

  • Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, Andre F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022 Mar 10;386(10):942-950. doi: 10.1056/NEJMoa2114663.

    PubMed 35263519

  • Burris HA, Chan A, Bardia A, Thaddeus Beck J, Sohn J, Neven P, Tripathy D, Im SA, Chia S, Esteva FJ, Hart L, Zarate JP, Ridolfi A, Lorenc KR, Yardley DA. Safety and impact of dose reductions on efficacy in the randomised MONALEESA-2, -3 and -7 trials in hormone receptor-positive, HER2-negative advanced breast cancer. Br J Cancer. 2021 Aug;125(5):679-686. doi: 10.1038/s41416-021-01415-9. Epub 2021 Jun 22.

    PubMed 34158598

  • Prat A, Chaudhury A, Solovieff N, Pare L, Martinez D, Chic N, Martinez-Saez O, Braso-Maristany F, Lteif A, Taran T, Babbar N, Su F. Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies. J Clin Oncol. 2021 May 1;39(13):1458-1467. doi: 10.1200/JCO.20.02977. Epub 2021 Mar 26.

    PubMed 33769862

  • Yardley DA. MONALEESA clinical program: a review of ribociclib use in different clinical settings. Future Oncol. 2019 Aug;15(23):2673-2686. doi: 10.2217/fon-2019-0130. Epub 2019 Jul 15.

    PubMed 31305131

  • Hortobagyi GN. Ribociclib for the first-line treatment of advanced hormone receptor-positive breast cancer: a review of subgroup analyses from the MONALEESA-2 trial. Breast Cancer Res. 2018 Oct 19;20(1):123. doi: 10.1186/s13058-018-1050-7.

    PubMed 30340505

  • Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018 Jul 1;29(7):1541-1547. doi: 10.1093/annonc/mdy155.

    PubMed 29718092

  • Janni W, Alba E, Bachelot T, Diab S, Gil-Gil M, Beck TJ, Ryvo L, Lopez R, Tsai M, Esteva FJ, Aunon PZ, Kral Z, Ward P, Richards P, Pluard TJ, Sutradhar S, Miller M, Campone M. First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial. Breast Cancer Res Treat. 2018 Jun;169(3):469-479. doi: 10.1007/s10549-017-4658-x. Epub 2018 Feb 5.

    PubMed 29404806

  • Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, Andre F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. doi: 10.1056/NEJMoa1609709. Epub 2016 Oct 7.

    PubMed 27717303

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ribociclib and Letrozole in people with Advanced, Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 221 sites in 29 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 221 sites in United States, Germany, Italy, France, Spain and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) by Investigator Assessment (time frame: Up to 23 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01958021, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2025.

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