NCT03096847

Brief Summary

This was a national, multi-center, open-label, phase IIIb trial to determine the efficacy and safety of treatment with ribociclib (LEE011) plus letrozole in patients with HR+, HER2-negative advanced (recurrent or metastatic) breast cancer. Patients were treated with daily doses of 600 mg ribociclib (3-weeks-on/1-week-off schedule) in combination with 2.5 mg letrozole daily (continuous dosing). Dose adjustments (dose reduction or interruption) according to safety findings were allowed.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
502

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Oct 2016

Typical duration for phase_3

Geographic Reach
1 country

84 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 24, 2016

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

March 10, 2017

Completed
20 days until next milestone

First Posted

Study publicly available on registry

March 30, 2017

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 11, 2018

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 6, 2020

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 19, 2021

Completed
Last Updated

October 11, 2021

Status Verified

October 1, 2021

Enrollment Period

2.1 years

First QC Date

March 10, 2017

Results QC Date

February 3, 2021

Last Update Submit

October 7, 2021

Conditions

Advanced Metastatic Breast Cancer

Keywords

ribociclibLEE011RIBECCAbreast cancerbreast carcinomaHR-positiveHER2-negativeadvanced breast cancerLetrozoleCDK4/6breast lumpHER2 positivemetastatic breast cancerbreast cancer positive for human epidermal growth factor receptor 2 (HER2) HER2 positive metastatic breast cancerbreast cancer progressionestrogen-receptor (ER) positive(+) breast cancerPaget's disease

Outcome Measures

Primary Outcomes (1)

  • Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole

    Clinical Benefit Rate (CBR) after 24 weeks of treatment as defined by RECIST 1.1 as percentage of patients with Complete Response (CR), Partial response (PR) or Stable disease (SD) lasting 24 weeks or longer as well as patients with Non-complete response, nonprogressive disease (NCRNPD).

    At 24 weeks after last patient enrolled in trial

Secondary Outcomes (10)

  • Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI)

    At week 24 , week 48 and week 72

  • Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months]

    Up to approximately month 25

  • Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI)

    At Week 24, Week 48 and Week 72

  • Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months]

    Up to approximatley 38 months

  • Overall Survival (OS) - Number of Censored Participants and Number of Deaths

    Up to approximatley 38 months

  • +5 more secondary outcomes

Study Arms (3)

ribociclib + letrozole cohort A

EXPERIMENTAL

ribociclib + letrozole cohort A - postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.

Drug: ribociclibDrug: letrozoleDrug: goserelin

ribociclib + letrozole cohort B1

EXPERIMENTAL

ribociclib + letrozole cohort B1 - premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly

Drug: ribociclibDrug: letrozoleDrug: goserelin

ribociclib + letrozole cohort B2

EXPERIMENTAL

ribociclib + letrozole cohort B2 - premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly

Drug: ribociclibDrug: letrozoleDrug: goserelin

Interventions

ribociclibDRUG

All patients with oestrogen receptor positive advanced or metastatic breast cancer were treated with oral ribociclib at a dose of 600mg daily and oral letrozole 2.5mg daily. The study treatment for an individual patient began on Study Day 1 and continued until 80 weeks after the last patient enrolled the study or until disease progression, unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occured first.

Also known as: LEE011
ribociclib + letrozole cohort Aribociclib + letrozole cohort B1ribociclib + letrozole cohort B2
letrozoleDRUG

All patients with oestrogen receptor positive advanced or metastatic breast cancer were treated with oral ribociclib at a dose of 600mg daily and oral letrozole 2.5mg daily. The study treatment for an individual patient began on Study Day 1 and continued until 80 weeks after the last patient enrolled the study or until disease progression, unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occured first.

ribociclib + letrozole cohort Aribociclib + letrozole cohort B1ribociclib + letrozole cohort B2
goserelinDRUG

Premenopausal patients additionally received goserelin 3.6mg as monthly implant

ribociclib + letrozole cohort Aribociclib + letrozole cohort B1ribociclib + letrozole cohort B2

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient is an adult, ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines
  • Women and men with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
  • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive and HER2-negative breast cancer by local laboratory. Local pathology is sufficient for assessment.
  • Patient must have either:
  • Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria ).
  • Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease
  • Non-measurable disease
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

You may not qualify if:

  • Patient who received any CDK4/6 inhibitor or any mTOR inhibitor.
  • Patient has a known hypersensitivity to any of the excipients of ribociclib or letrozole
  • Patients with current inflammatory breast cancer.
  • Patient has received \> 1 chemotherapy for the treatment of advanced/metastatic breast cancer
  • Patient has received \> 2 endocrine therapies for the treatment of advanced/metastatic breast cancer
  • Patient has central nervous system (CNS) involvement. If patient is fulfilling the following 3 criteria she/he is eligible for the trial.
  • completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of study and
  • CNS tumor is clinically stable at the time of screening and
  • Patient is not receiving steroids and enzyme inducing anti-epileptic medications for brain metastases
  • Patient has active cardiac disease or a history of cardiac dysfunction

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (84)

Novartis Investigative Site

Munich, Bavaria, 80335, Germany

Location

Novartis Investigative Site

Langen, Hesse, 63225, Germany

Location

Novartis Investigative Site

Recklinghausen, North Rhine-Westphalia, 45657, Germany

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Novartis Investigative Site

Lübeck, Schleswig-Holstein, 23563, Germany

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Novartis Investigative Site

Aachen, 52074, Germany

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Novartis Investigative Site

Augsburg, 86150, Germany

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Novartis Investigative Site

Berlin, 10117, Germany

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Novartis Investigative Site

Berlin, 10367, Germany

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Novartis Investigative Site

Berlin, 10713, Germany

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Novartis Investigative Site

Berlin, 10967, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Berlin, 13581, Germany

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Novartis Investigative Site

Berlin, 14195, Germany

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Novartis Investigative Site

Bielefeld, 33604, Germany

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Novartis Investigative Site

Bonn, 53111, Germany

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Novartis Investigative Site

Bottrop, 46236, Germany

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Novartis Investigative Site

Böblingen, 71032, Germany

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Novartis Investigative Site

Chemnitz, 09113, Germany

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Novartis Investigative Site

Cologne, 50935, Germany

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Novartis Investigative Site

Dessau, 06847, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Düsseldorf, 40225, Germany

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Novartis Investigative Site

Düsseldorf, 40479, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Essen, 45136, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Esslingen am Neckar, 73730, Germany

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Novartis Investigative Site

Frankfurt, 60398, Germany

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Novartis Investigative Site

Frankfurt, 60431, Germany

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Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Fürstenwalde, 15517, Germany

Location

Novartis Investigative Site

Fürth, 90766, Germany

Location

Novartis Investigative Site

Georgsmarienhütte, 49124, Germany

Location

Novartis Investigative Site

Goslar, 38642, Germany

Location

Novartis Investigative Site

Göttingen, 37073, Germany

Location

Novartis Investigative Site

Greifswald, 17475, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Hamburg, 22081, Germany

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Novartis Investigative Site

Hamburg, 22767, Germany

Location

Novartis Investigative Site

Hanover, 30177, Germany

Location

Novartis Investigative Site

Hanover, 30559, Germany

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Novartis Investigative Site

Hanover, 30625, Germany

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Novartis Investigative Site

Heidelberg, 69115, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Hildesheim, 31134, Germany

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Novartis Investigative Site

Homburg, 66421, Germany

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Novartis Investigative Site

Jena, 07740, Germany

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Novartis Investigative Site

Kiel, 24103, Germany

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Novartis Investigative Site

Kiel, 24105, Germany

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Novartis Investigative Site

Kulmbach, 95326, Germany

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Novartis Investigative Site

Landshut, 84028, Germany

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Novartis Investigative Site

Leer, 26789, Germany

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Novartis Investigative Site

Leipzig, 04103, Germany

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Novartis Investigative Site

Leipzig, 04277, Germany

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Novartis Investigative Site

Mannheim, 68165, Germany

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Novartis Investigative Site

Marburg, 35037, Germany

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Novartis Investigative Site

Minden, 32429, Germany

Location

Novartis Investigative Site

Mönchengladbach, 41061, Germany

Location

Novartis Investigative Site

München, 80637, Germany

Location

Novartis Investigative Site

Münster, 48145, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

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Novartis Investigative Site

Neuruppin, 16816, Germany

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Novartis Investigative Site

Nuremberg, 90419, Germany

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Novartis Investigative Site

Offenbach, 63069, Germany

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Novartis Investigative Site

Oldenburg, 26121, Germany

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Novartis Investigative Site

Passau, 94032, Germany

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Novartis Investigative Site

Potsdam, 14467, Germany

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Novartis Investigative Site

Ravensburg, 88214, Germany

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Novartis Investigative Site

Rotenburg (Wümme), 27356, Germany

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Novartis Investigative Site

Saarbrücken, 66113, Germany

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Novartis Investigative Site

Schweinfurt, 97422, Germany

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Novartis Investigative Site

Stuttgart, 70199, Germany

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Novartis Investigative Site

Suhl, 98527, Germany

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Novartis Investigative Site

Torgau, 04860, Germany

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Novartis Investigative Site

Trier, 54290, Germany

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Novartis Investigative Site

Troisdorf, 53840, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Ulm, 89081, Germany

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Novartis Investigative Site

Velbert, 42551, Germany

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Novartis Investigative Site

Völklingen, 66333, Germany

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Novartis Investigative Site

Weinheim, 69469, Germany

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Novartis Investigative Site

Wetzlar, 35578, Germany

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Novartis Investigative Site

Wiesbaden, 65191, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Related Publications (1)

  • Peuker CA, Yaghobramzi S, Grunert C, Keilholz L, Gjerga E, Hennig S, Schaper S, Na IK, Keller U, Brucker S, Decker T, Fasching P, Fehm T, Janni W, Kummel S, Schneeweiss A, Schuler M, Luftner D, Busse A. Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer-findings from the RIBECCA trial. Eur J Cancer. 2022 Feb;162:45-55. doi: 10.1016/j.ejca.2021.11.025. Epub 2021 Dec 23.

    PMID: 34953442DERIVED

Related Links

MeSH Terms

Conditions

Breast NeoplasmsOsteitis Deformans

Interventions

ribociclibLetrozoleGoserelin

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesBone DiseasesMusculoskeletal Diseases

Intervention Hierarchy (Ancestors)

NitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsGonadotropin-Releasing HormonePituitary Hormone-Releasing HormonesHypothalamic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteins

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
Novartis.email@Novartis.com
+ 1 862 778 8300

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 10, 2017

First Posted

March 30, 2017

Study Start

October 24, 2016

Primary Completion

December 11, 2018

Study Completion

February 6, 2020

Last Updated

October 11, 2021

Results First Posted

May 19, 2021

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will share

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 review 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 availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

More information

Locations

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