Study for Women and Men With Hormone-receptor Positive Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT03096847

Last Updated: 2021-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 502 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-24
• Study Completion Date: 2020-02-06

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.

Detailed Description

The main purpose of this study was to collect additional efficacy and safety data for the combination of ribociclib and letrozole in a patient population broader than the MONALEESA-2 study (NCT01958021 / CLEE011A2301), and to provide access to ribociclib to patients for which available treatment options are unsatisfactory treatment alternatives until the drug is approved for this indication. Furthermore, this trial aimed to collect data for the combination of ribociclib and letrozole in the context of current local routine therapy algorithms for the treatment of metastatic and advanced breast cancer.

This multi-center, open-label, single-arm study aimed to evaluate the efficacy, safety, and quality of life for the combination of ribociclib and letrozole in a patient population than in the MONALEESA-2 study, i.e. in patients pretreated with one line of chemotherapy and/or a maximum of two lines of endocrine therapy as well as premenopausal patients, without limitations regarding the disease free interval after adjuvant therapy.

For ethical reasons no endocrine comparator drugs were investigated in this study. The duration of study treatment of 80 weeks was adequate to determine the primary, secondary and exploratory study parameters. The sample size was suitable to estimate the clinical benefit rate (CBR) in this patient population with reasonable precision.

Goserelin was used in premenopausal patients, since it was shown that ovarian suppression of estrogen release with luteinizing hormone-releasing hormone agonists (LHRHa) (such as goserelin) is effective in preventing relapse in premenopausal women with early stage ER+ breast cancer (Klijn et al. 2001).

The efficacy and safety of ribociclib in combination with letrozole for the treatment of postmenopausal women with advanced or metastatic breast cancer vs. placebo (i.e., letrozole alone) was already demonstrated in the preceding, pivotal MONALESSA-2 study. Thus, for ethical reasons no endocrine comparator drugs were investigated in the present RIBECCA study.

Generally, the single-arm, open-label design and the broadening of the study population (compared to the pivotal MONALESSA-2 study) in the RIBECCA study was deemed appropriate to further evaluate the efficacy and safety of ribociclib plus letrozole among breast cancer patients in a treatment setting closer to routine care. The duration of study treatment of up to 80 weeks was considered adequate to determine the primary, secondary and exploratory study parameters. Moreover, the sample size was suitable to estimate the CBR in this patient population with reasonable precision.

Conditions

Advanced Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ribociclib + letrozole cohort A

ribociclib + letrozole cohort A - postmenopausal women, or men; naïve.

All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.

Group Type: EXPERIMENTAL

ribociclib

Intervention Type: DRUG

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.

letrozole

Intervention Type: DRUG

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.

goserelin

Intervention Type: DRUG

Premenopausal patients additionally received goserelin 3.6mg as monthly implant

ribociclib + letrozole cohort B1

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

Group Type: EXPERIMENTAL

ribociclib

Intervention Type: DRUG

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.

letrozole

Intervention Type: DRUG

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.

goserelin

Intervention Type: DRUG

Premenopausal patients additionally received goserelin 3.6mg as monthly implant

ribociclib + letrozole cohort B2

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

Group Type: EXPERIMENTAL

ribociclib

Intervention Type: DRUG

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.

letrozole

Intervention Type: DRUG

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.

goserelin

Intervention Type: DRUG

Premenopausal patients additionally received goserelin 3.6mg as monthly implant

Interventions

ribociclib

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.

Intervention Type: DRUG

letrozole

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.

Intervention Type: DRUG

goserelin

Premenopausal patients additionally received goserelin 3.6mg as monthly implant

Intervention Type: DRUG

Other Intervention Names

LEE011

Eligibility Criteria

Inclusion Criteria

• 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:

1. Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria ).

2. Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease

3. Non-measurable disease

• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

Exclusion Criteria

• 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.

1. completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of study and

2. CNS tumor is clinically stable at the time of screening and

3. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Munich, Bavaria, Germany

Novartis Investigative Site

Langen, Hesse, Germany

Novartis Investigative Site

Recklinghausen, North Rhine-Westphalia, Germany

Novartis Investigative Site

Lübeck, Schleswig-Holstein, Germany

Novartis Investigative Site

Aachen, , Germany

Novartis Investigative Site

Augsburg, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Bielefeld, , Germany

Novartis Investigative Site

Bonn, , Germany

Novartis Investigative Site

Bottrop, , Germany

Novartis Investigative Site

Böblingen, , Germany

Novartis Investigative Site

Chemnitz, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Dessau, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Düsseldorf, , Germany

Novartis Investigative Site

Düsseldorf, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Esslingen am Neckar, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Freiburg im Breisgau, , Germany

Novartis Investigative Site

Fürstenwalde, , Germany

Novartis Investigative Site

Fürth, , Germany

Novartis Investigative Site

Georgsmarienhütte, , Germany

Novartis Investigative Site

Goslar, , Germany

Novartis Investigative Site

Göttingen, , Germany

Novartis Investigative Site

Greifswald, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Hildesheim, , Germany

Novartis Investigative Site

Homburg, , Germany

Novartis Investigative Site

Jena, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Kulmbach, , Germany

Novartis Investigative Site

Landshut, , Germany

Novartis Investigative Site

Leer, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Mannheim, , Germany

Novartis Investigative Site

Marburg, , Germany

Novartis Investigative Site

Minden, , Germany

Novartis Investigative Site

Mönchengladbach, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Neuruppin, , Germany

Novartis Investigative Site

Nuremberg, , Germany

Novartis Investigative Site

Offenbach, , Germany

Novartis Investigative Site

Oldenburg, , Germany

Novartis Investigative Site

Passau, , Germany

Novartis Investigative Site

Potsdam, , Germany

Novartis Investigative Site

Ravensburg, , Germany

Novartis Investigative Site

Rotenburg (Wümme), , Germany

Novartis Investigative Site

Saarbrücken, , Germany

Novartis Investigative Site

Schweinfurt, , Germany

Novartis Investigative Site

Stuttgart, , Germany

Novartis Investigative Site

Suhl, , Germany

Novartis Investigative Site

Torgau, , Germany

Novartis Investigative Site

Trier, , Germany

Novartis Investigative Site

Troisdorf, , Germany

Novartis Investigative Site

Tübingen, , Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Velbert, , Germany

Novartis Investigative Site

Völklingen, , Germany

Novartis Investigative Site

Weinheim, , Germany

Novartis Investigative Site

Wetzlar, , Germany

Novartis Investigative Site

Wiesbaden, , Germany

Novartis Investigative Site

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 34953442 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=729

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

CLEE011XDE01

Identifier Type: OTHER

Identifier Source: secondary_id

2016-002556-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLEE011XDE01

Identifier Type: -

Identifier Source: org_study_id