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AzTrials

Advanced Breast CancerPhase 3MONALEESA-3NCT02422615

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

A Phase 3 study testing Ribociclib and Fulvestrant in people with Advanced Breast Cancer, run by Novartis Pharmaceuticals at 174 sites in 30 countries.

Completed

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

Official record
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Trial summary

The main aim of this study was to evaluate the efficacy and safety of adding ribociclib to fulvestrant in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Breast Cancer
What is being tested?
Ribociclib and Fulvestrant
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
726 participants
Where
174 sitesin 30 countries
Study dates
9 Jun 2015to 11 Jan 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients were adults, both male and female, aged ≥ 18 years at the time of providing informed consent. Female patients were required to be postmenopausal. Informed consent was obtained prior to any trial-related activities, following local guidelines.
  • Patients had a confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer, determined through histological and/or cytological examination by a local laboratory. Patients also had HER2-negative breast cancer.
  • Patients had either measurable disease as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion.
  • Patients had advanced breast cancer, which included locoregionally recurrent disease not amenable to curative therapies (such as surgery or radiotherapy) or metastatic breast cancer. Patients fell into one of the following categories:
  • Newly diagnosed with advanced/metastatic breast cancer and treatment-naïve.
  • Relapsed with documented evidence of relapse more than 12 months after completing (neo)adjuvant endocrine therapy, without any prior treatment for advanced/metastatic disease.
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  • Relapsed with documented evidence of relapse on or within 12 months from completing (neo)adjuvant endocrine therapy, without any prior treatment for advanced/metastatic disease.
  • Relapsed with documented evidence of relapse more than 12 months after completing adjuvant endocrine therapy and subsequently progressed after receiving one line of endocrine therapy (antiestrogen or aromatase inhibitor) for advanced/metastatic disease.
  • Newly diagnosed with advanced/metastatic breast cancer at diagnosis and progressed after receiving one line of endocrine therapy (antiestrogen or aromatase inhibitor), with documented evidence of progression.
  • Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Patients had adequate bone marrow and organ function.

Who cannot join

  • Patients with symptomatic visceral disease or disease burden that rendered them ineligible for endocrine therapy, based on the investigator's judgment.
  • 2. Patients who had received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), fulvestrant, or any CDK4/6 inhibitor.
  • 3. Patients with inflammatory breast cancer at the screening stage. 4. Patients with central nervous system (CNS) involvement, unless they were at least 4 weeks from completing prior therapy before initiating the study treatment and had a stable CNS tumor at the time of screening. They were also required not to be receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
  • 5. Patients with clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
  • 6. Patients who were currently receiving any of the following substances, which could not be discontinued 7 days prior to initiating treatment:
  • Known strong inducers or inhibitors of CYP3A4/5.
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  • Substances with a known risk of prolonging the QT interval or inducing Torsades de Pointes.
  • Substances with a narrow therapeutic window and predominantly metabolized through CYP3A4/5.
  • Herbal preparations/medications, dietary supplements.

Trial locations and contacts

174 sites in 30 countries.

174 sites in 30 countries

United States26 sites

  • University of New Mexico Cancer Center SC

    Albuquerque, New Mexico, 87131

  • Ironwood Cancer and Research Centers SC-2

    Chandler, Arizona, 85224

  • Florida Cancer Research Institute Dept of Oncology

    Davie, Florida, 33328

  • Providence Regional Cancer Partnership .

    Everett, Washington, 98201

  • Highlands Oncology Group .

    Fayetteville, Arkansas, 72703

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80528

  • CR Wood Cancer Center SC

    Glens Falls, New York, 12801

  • Penn State University Milton S Hershey Medical Center SC

    Hershey, Pennsylvania, 17033

  • Moanalua Medical Center. Attn: Oncology Dept SC

    Honolulu, Hawaii, 96817

  • Millennium Research Clin Develop SC

    Houston, Texas, 77090

  • Jackson Oncology Associates SC

    Jackson, Mississippi, 39202

  • Providence Regional Cancer System SC

    Lacey, Washington, 98503

  • Clinical Research Alliance .

    Lake Success, New York, 11042

  • UCLA Medical Center .

    Los Angeles, California, 90095

  • Southern Cancer Center PC SC-2

    Mobile, Alabama, 36608

  • Meridian Health Systems Regulatory

    Neptune City, New Jersey, 07753

  • NYU Langone Med Center CV Research NYU Langone Medical Center

    New York, New York, 10016

  • Northern Utah Cancer Associates CFTY720DUS01

    Ogden, Utah, 84403-3105

  • Florida Hospital Cancer Institute SC

    Orlando, Florida, 32804

  • UF Health Cancer Center at Orlando Health

    Orlando, Florida, 32806

  • Oncology Specialists, SC Advocate Medical Group-Niles

    Park Ridge, Illinois, 60068-0736

  • Central Coast Medical Oncology Corporation SC

    Santa Maria, California, 93454

  • St Joseph Heritage Healthcare

    Santa Rosa, California, 94503

  • Virginia Mason Medical Center-Oncology SC

    Seattle, Washington, 98101

  • John D Archbold Memorial Hospital Main

    Thomasville, Georgia, 31792

  • Genesis Cancer Services SC

    Zanesville, Ohio, 43701

Other trials in United States

Germany25 sites

  • Novartis Investigative Site

    Augsburg, 86150

  • Novartis Investigative Site

    Berlin, 10117

  • Novartis Investigative Site

    Berlin, 10967

  • Novartis Investigative Site

    Bielefeld, 33604

  • Novartis Investigative Site

    Bonn, 53111

  • Novartis Investigative Site

    Cologne, 50935

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Fürth, 90766

  • Novartis Investigative Site

    Georgsmarienhütte, Lower Saxony, 49124

  • Novartis Investigative Site

    Hamburg, 22081

  • Novartis Investigative Site

    Hamburg, 22767

  • Novartis Investigative Site

    Hanover, 30559

  • Novartis Investigative Site

    Heidelberg, 69115

  • Novartis Investigative Site

    Langen, Hesse, 63225

  • Novartis Investigative Site

    Lübeck, 23538

  • Novartis Investigative Site

    Mühlhausen, 99974

  • Novartis Investigative Site

    München, 80637

  • Novartis Investigative Site

    Oldenburg, 26121

  • Novartis Investigative Site

    Ravensburg, 88214

  • Novartis Investigative Site

    Saarbrücken, 66113

  • Novartis Investigative Site

    Troisdorf, 53840

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Velbert, 42551

  • Novartis Investigative Site

    Weiden, 92637

Other trials in Germany

France14 sites

  • Novartis Investigative Site

    Besançon, 25030

  • Novartis Investigative Site

    Bordeaux, 33000

  • Novartis Investigative Site

    Bordeaux, 33076

  • Novartis Investigative Site

    Brest, 29200

  • Novartis Investigative Site

    Créteil, 94000

  • Novartis Investigative Site

    Le Mans, 72015

  • Novartis Investigative Site

    Lille, 59020

  • Novartis Investigative Site

    Limoges, 87000

  • Novartis Investigative Site

    Paris, 75651

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Reims, Marne, 51056

  • Novartis Investigative Site

    Saint-Cloud, Hauts De Seine, 92210

  • Novartis Investigative Site

    Strasbourg, Cedex, 67000

  • Novartis Investigative Site

    Toulon La Seyne Sur Mer, 83056

Other trials in France

Canada12 sites

  • Novartis Investigative Site

    Brampton, Ontario, L6R 3J7

  • Novartis Investigative Site

    Halifax, Nova Scotia, B3H 1V7

  • Novartis Investigative Site

    Kingston, Ontario, K7L 5P9

  • Novartis Investigative Site

    Moncton, New Brunswick, E1C 8X3

  • Novartis Investigative Site

    Montreal, Quebec, H3G 1L5

  • Novartis Investigative Site

    Newmarket, Ontario, J7Y 2P9

  • Novartis Investigative Site

    Rimouski, Quebec, G5L 5T1

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    Surrey, British Columbia, V3V 1Z2

  • Novartis Investigative Site

    Trois-Rivières, Quebec, G8Z 3R9

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E6

  • Novartis Investigative Site

    Victoria, British Columbia, V8R 6V5

Other trials in Canada

Netherlands12 sites

  • Novartis Investigative Site

    Amsterdam, 1066 CX

  • Novartis Investigative Site

    Breda, 4819 EV

  • Novartis Investigative Site

    Deventer, 7416 SE

  • Novartis Investigative Site

    Enschede, 7513 ER

  • Novartis Investigative Site

    Groningen, 9728 NZ

  • Novartis Investigative Site

    Hoofddorp, 2134 TM

  • Novartis Investigative Site

    Maastricht, 6229 HX

  • Novartis Investigative Site

    Nieuwegein, 3435 CM

  • Novartis Investigative Site

    Roermond, 6043 CV

  • Novartis Investigative Site

    Sittard-Geleen, 6162 BG

  • Novartis Investigative Site

    The Hague, 2545 CH

  • Novartis Investigative Site

    Tilburg, 5042 AD

Other trials in Netherlands

Spain12 sites

  • Novartis Investigative Site

    A Coruña, Galicia, 15009

  • Novartis Investigative Site

    Alcorcón, Madrid, 28922

  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

  • Novartis Investigative Site

    Granada, Andalusia, 18014

  • Novartis Investigative Site

    Madrid, Andalusia, 28046

  • Novartis Investigative Site

    Madrid, 28009

  • Novartis Investigative Site

    Madrid, 28222

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

  • Novartis Investigative Site

    Salamanca, Castille and León, 37007

  • Novartis Investigative Site

    San Sebastián de los Reyes, Madrid, 28702

  • Novartis Investigative Site

    Sant Joan Despí, Barcelona, 08970

  • Novartis Investigative Site

    Seville, Andalusia, 41014

Other trials in Spain

Italy8 sites

  • Novartis Investigative Site

    Brescia, BS, 25123

  • Novartis Investigative Site

    Catania, CT, 95124

  • Novartis Investigative Site

    L’Aquila, AQ, 67100

  • Novartis Investigative Site

    Lecce, LE, 73100

  • Novartis Investigative Site

    Milan, MI, 20133

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Pontedera, PI, 56025

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Belgium6 sites

  • Novartis Investigative Site

    Aalst, 9300

  • Novartis Investigative Site

    Charleroi, 6000

  • Novartis Investigative Site

    Hasselt, 3500

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Liège, 4000

  • Novartis Investigative Site

    Namur, 5000

Other trials in Belgium

Denmark6 sites

  • Novartis Investigative Site

    Aalborg, DK 9000

  • Novartis Investigative Site

    Aarhus, DK-8000

  • Novartis Investigative Site

    Copenhagen, DK-2100

  • Novartis Investigative Site

    Herlev, 2730

  • Novartis Investigative Site

    Odense C, DK 5000

  • Novartis Investigative Site

    Vejle, 7100

Other trials in Denmark

Czechia5 sites

  • Novartis Investigative Site

    Brno, 65653

  • Novartis Investigative Site

    Brno-Bohunice, Czech Republic, 625 00

  • Novartis Investigative Site

    Liberec, Czech Republic, 46063

  • Novartis Investigative Site

    Prague, 12808

  • Novartis Investigative Site

    Prague, 180 81

Other trials in Czechia

Hungary5 sites

  • Novartis Investigative Site

    Budapest, 1134

  • Novartis Investigative Site

    Budapest, H 1122

  • Novartis Investigative Site

    Budapest, H-1032

  • Novartis Investigative Site

    Debrecen, 4032

  • Novartis Investigative Site

    Szolnok, H-5000

Other trials in Hungary

Australia4 sites

  • Novartis Investigative Site

    East Melbourne, Victoria, 3002

  • Novartis Investigative Site

    Herston, Queensland, 4029

  • Novartis Investigative Site

    Nedlands, Western Australia, 6009

  • Novartis Investigative Site

    St Leonards, New South Wales, 2065

Other trials in Australia

Turkey (Türkiye)4 sites

  • Novartis Investigative Site

    Istanbul, 34303

  • Novartis Investigative Site

    Istanbul, 34381

  • Novartis Investigative Site

    Istanbul, 34662

  • Novartis Investigative Site

    Izmir, 35575

Other trials in Turkey (Türkiye)

Austria3 sites

  • Novartis Investigative Site

    Innsbruck, Tyrol, 6020

  • Novartis Investigative Site

    Vienna, A-1090

  • Novartis Investigative Site

    Vienna, A-1100

Other trials in Austria

Bulgaria3 sites

  • Novartis Investigative Site

    Sofia, 1303

  • Novartis Investigative Site

    Sofia, 1606

  • Novartis Investigative Site

    Sofia, 1756

Other trials in Bulgaria

South Korea3 sites

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 03722

  • Novartis Investigative Site

    Seoul, 06351

Other trials in South Korea

Sweden3 sites

  • Novartis Investigative Site

    Eskilstuna, SE-631 88

  • Novartis Investigative Site

    Sundsvall, 851 86

  • Novartis Investigative Site

    Vaxjo, SE-351 85

Other trials in Sweden

Switzerland3 sites

  • Novartis Investigative Site

    Aarau, 5000

  • Novartis Investigative Site

    Basel, 4031

  • Novartis Investigative Site

    Zurich, 8038

Other trials in Switzerland

Colombia2 sites

  • Novartis Investigative Site

    Bogotá, 110221

  • Novartis Investigative Site

    Montería, 230004

Other trials in Colombia

Lebanon2 sites

  • Novartis Investigative Site

    Beirut, 1107 2020

  • Novartis Investigative Site

    El Achrafiyé, 166830

Other trials in Lebanon

Malaysia2 sites

  • Novartis Investigative Site

    Johor Bahru, Johor, 81100

  • Novartis Investigative Site

    Kuching, Sarawak, 93586

Other trials in Malaysia

Poland2 sites

  • Novartis Investigative Site

    Konin, 62 500

  • Novartis Investigative Site

    Warsaw, 04-125

Other trials in Poland

Portugal2 sites

  • Novartis Investigative Site

    Lisbon, 1400-038

  • Novartis Investigative Site

    Porto, 4200-072

Other trials in Portugal

Russia2 sites

  • Novartis Investigative Site

    Arkhangelsk, 163045

  • Novartis Investigative Site

    Tambov, 392000

Other trials in Russia

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Bangkok, 10400

Other trials in Thailand

United Kingdom2 sites

  • Novartis Investigative Site

    Newcastle upon Tyne, NE7 7DN

  • Novartis Investigative Site

    Plymouth, Devon, PL6 8DH

Other trials in United Kingdom

Jordan1 site

  • Novartis Investigative Site

    Amman, 11941

Other trials in Jordan

Mexico1 site

  • Novartis Investigative Site

    Oaxaca City, 68000

Other trials in Mexico

Norway1 site

  • Novartis Investigative Site

    Oslo, NO 0424

Other trials in Norway

Singapore1 site

  • Novartis Investigative Site

    Singapore, 119228

Other trials in Singapore

About this study

Official title: A Randomized Double-blind, Placebo-controlled Study of Ribociclib in Combination With Fulvestrant for the Treatment of Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Who Have Received no or Only One Line of Prior Endocrine Treatment

The main aim of this study was to evaluate the efficacy and safety of adding ribociclib to fulvestrant in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer.

Read the detailed description

This study was a randomized, phase III, double-blind, placebo-controlled international trial aimed at determining the efficacy and safety of treatment with fulvestrant in combination with ribociclib compared to fulvestrant with placebo in men and postmenopausal women diagnosed with HR+, HER2-negative advanced breast cancer. The study comprised four phases: screening (up to 28 days), randomized treatment, post-treatment disease progression follow-up, and post-treatment survival follow-up.

Enrolled participants were randomly assigned to receive either fulvestrant+ribociclib or fulvestrant+placebo in a ratio of 2:1. The randomization process was stratified based on the presence of liver and/or lung metastases (yes versus no) and prior endocrine therapy. Treatment was administered until disease progression, occurrence of unacceptable toxicity, or discontinuation from the study treatment for other reasons.

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.

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

A protocol amendment 4 (dated 29-Jan-2020) allowed for unblinding of study participants, and those still receiving placebo had the option to switch to the ribociclib arm. The decision for crossover was made at the investigator's discretion and required patient consent.

Being tested
Ribociclib, Fulvestrant, Placebo
Keywords
HR-positive, HER2-negative, Advanced breast cancer, LEE011, ribociclib, fulvestrant, faslodex, CDK, CDK4, CDK6, CDK4/6, CDK4/6 inhibitor, Phase III, ER-positive, PR-positive, Postmenopausal, Men, Breast Neoplasms, Breast Diseases, Neoplasms
Medical subject headings
Multiple Endocrine Neoplasia Type 1, Breast Neoplasms, Breast Diseases, Neoplasms, Neoplasms by Site

What participants receive

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

  • RibociclibDrug

    Also called LEE011

    Ribociclib capsules were administered orally at a daily dose of 600mg for 21 consecutive days within a 28-day cycle.

  • FulvestrantDrug

    Fulvestrant was administered via intramuscular injections at a dose of 500mg every 28 days, starting on Day 1 of each cycle. In Cycle 1, an additional dose of Fulvestrant was given on Day 15.

  • PlaceboDrug

    Placebo capsules were administered orally for 21 consecutive days within a 28-day cycle.

Study groups in NCT02422615
Study groupRoleWhat they receive
Ribociclib + fulvestrantExperimentalRibociclib was administered orally at a daily dose of 600mg for 21 consecutive days within a 28-day cycle. This treatment was combined with fulvestrant, which was administered via intramuscular injections of 500mg every 28 days starting on Day 1 of each cycle. Additionally, an extra dose of fulvestrant was given on Day 15 of Cycle 1. For participants who did not tolerate the protocol-specified dosing schedule, dose adjustments were permitted in order to allow the patient to continue the study treatment.
Receives: Drug: Ribociclib; Drug: Fulvestrant
Placebo + fulvestrantPlacebo comparatorPlacebo was administered orally for 21 consecutive days within a 28-day cycle. This treatment was combined with fulvestrant, which was administered via intramuscular injections of 500mg every 28 days starting on Day 1 of each cycle. Additionally, an extra dose of fulvestrant was given on Day 15 of Cycle 1. For participants who did not tolerate the protocol-specified dosing schedule, dose adjustments were permitted in order to allow the patient to continue the study treatment. Participants were unblinded after the implementation of protocol amendment 4 (29-Jan-20) and were given the option to crossover to treatment with ribociclib and fulvestrant.
Receives: Drug: Fulvestrant; Drug: Placebo

What is being measured

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

  1. Progression Free Survival (PFS) Per 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 via local radiology 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.

    The distribution of PFS between the two arms was compared using a stratified log-rank test at a one-sided 2.5% level of significance. The PFS hazard ratio with two-sided 95% confidence interval was derived from the stratified Cox proportional hazards model.

    Measured: From randomization to first documented progression or death, assessed up to approximately 26 months

Secondary outcomes (11)

  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. As per protocol, the final OS analysis was conducted after approximately 351 deaths were documented.

    OS was estimated using the Kaplan-Meier method. The median OS, along with 95% confidence intervals (CIs), 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: From randomization to death, assessed up to approximately 46 months

  2. Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC)

    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 via BIRC 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.

    Measured: From randomization to first documented progression or death, assessed up to approximately 26 months

  3. Overall Response Rate (ORR) Per Investigator Assessment

    ORR was defined as 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 lesions with lymph nodes measuring < 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 approximately 26 months

  4. Clinical Benefit Rate (CBR) Per Investigator Assessment

    CBR was defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1 as per investigator assessment.

    CR: Disappearance of all lesions with lymph nodes measuring < 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.

    Measured: Up to approximately 26 months

  5. Time to Response (TTR) Per Investigator Assessment

    TTR was defined as the time from randomization to the first documented and confirmed response (CR or PR) as defined by RECIST 1.1 per investigator assessment. The Kaplan-Meier method was used to estimate TTR, and the median TTR, along with 95% confidence intervals, was reported for each treatment group. Participants who did not achieve a confirmed response were censored at the maximum follow-up time for patients who had a PFS event (i.e. either progressed or died due to any cause) or at the date of last adequate tumor assessment otherwise.

    CR: Disappearance of all lesions with lymph nodes measuring < 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: From randomization to first response, assessed up to approximately 26 months

  6. Duration of Response (DOR) Per Investigator Assessment

    DOR was defined as the time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer as defined in RECIST 1.1 per investigator assessment. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals, was reported for each treatment group. If a participant had not had an event, duration was censored at the date of last adequate tumor assessment.

    CR: Disappearance of all lesions with lymph nodes measuring < 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: From first documented response to progression or death, assessed up to approximately 26 months

  7. Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) in One Score Category

    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: Up to approximately 26 months

  8. 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, a GHS/QoL scale, and 6 single items. GHS/QoL scale scores range 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: Up to approximately 26 months

  9. 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, a GHS/QoL scale, and 6 single items. GHS/QoL scale scores range 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 assessed. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits occurred every 8 weeks during the initial 18 months since start of treatment, followed by visits every 12 weeks until disease progression.

    Measured: Baseline, every 8 weeks after randomization during 18 months, then every 12 weeks up to end of treatment; end of treatment; and every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to approximately 26 months

  10. Ribociclib Plasma Concentrations

    Blood samples were collected to assess the concentration by time point for ribociclib. Participants were classified into the following dose groups at each timepoint: 1) ribociclib 600 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 600 mg immediately prior to the blood collection without a dose change or interruption. 2) ribociclib 400 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 400 mg immediately prior to the blood collection without a dose change or interruption. 3) ribociclib 200 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 200 mg immediately prior to the blood collection without a dose change or interruption.

    Measured: Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle=28 days

  11. LEQ803 Plasma Concentrations

    Blood samples were collected to assess the concentration by time point for LEQ803, a metabolite of ribociclib. Participants were classified into the following dose groups at each timepoint: 1) ribociclib 600 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 600 mg immediately prior to the blood collection without a dose change or interruption. 2) ribociclib 400 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 400 mg immediately prior to the blood collection without a dose change or interruption. 3) ribociclib 200 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 200 mg immediately prior to the blood collection without a dose change or interruption.

    Measured: Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. 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 posted21 Apr 2015 (estimated)
  2. Study start9 Jun 2015
  3. Primary completion3 Nov 2017
  4. Study completion11 Jan 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
Model description
Following protocol amendment 4 (29-Jan-2020), study participants were unblinded, with an opportunity for those patients still in the study in the arm of placebo + fulvestrant to transition to the treatment of ribociclib + fulvestrant.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
726 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02422615
Sponsor's protocol ID
CLEE011F2301
Other IDs
2015-000617-43, 2015
Acronym
MONALEESA-3
Status last verified
Nov 2023
First submitted
1 Apr 2015
Last updated
30 Nov 2023
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

  • Hart LL, Im SA, Tolaney SM, Campone M, Pluard T, Sousa B, Freyer G, Decker T, Kalinsky K, Sopher G, Gao M, Hu H, Kuemmel S. Efficacy, safety, and patient-reported outcomes across young to older age groups of patients with HR+/HER2- advanced breast cancer treated with ribociclib plus endocrine therapy in the randomized MONALEESA-2, -3, and -7 trials. Eur J Cancer. 2025 Feb 25;217:115225. doi: 10.1016/j.ejca.2025.115225. Epub 2025 Jan 8.

    PubMed 39826197

  • 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

  • Neven P, Fasching PA, Chia S, Jerusalem G, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Zarate JP, Wang Y, Chakravartty A, Wang C, Slamon DJ. Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant. Breast Cancer Res. 2023 Aug 31;25(1):103. doi: 10.1186/s13058-023-01701-9.

    PubMed 37653397

  • 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

  • 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

  • Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, Petrakova K, Valeria Bianchi G, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Ji Y, Wang C, Deore U, Chakravartty A, Zarate JP, Taran T, Fasching PA. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021 Aug;32(8):1015-1024. doi: 10.1016/j.annonc.2021.05.353. Epub 2021 Jun 5.

    PubMed 34102253

  • 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

  • Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020 Feb 6;382(6):514-524. doi: 10.1056/NEJMoa1911149. Epub 2019 Dec 11.

    PubMed 31826360

  • 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

  • Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. doi: 10.1200/JCO.2018.78.9909. Epub 2018 Jun 3.

    PubMed 29860922

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ribociclib and Fulvestrant in people with Advanced Breast Cancer, run by Novartis Pharmaceuticals at 174 sites in 30 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 9 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 30 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 174 sites in United States, Germany, France, Canada, Netherlands and 25 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 19 Sep 2018). 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) Per Investigator Assessment (time frame: From randomization to first documented progression or death, assessed up to approximately 26 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 NCT02422615, which also lists 11 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 30 Nov 2023.

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