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Advanced Metastatic Breast CancerPhase 3NCT03096847

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

A Phase 3 study testing ribociclib, letrozole and goserelin in people with Advanced Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 84 sites in Germany.

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

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Advanced Metastatic Breast Cancer
What is being tested?
ribociclib, letrozole and goserelin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
502 participants
Where
84 sitesGermany
Study dates
24 Oct 2016to 6 Feb 2020
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 10Show fewer
  • 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

Trial locations and contacts

84 sites in 1 country.

84 sites in 1 country

Germany84 sites

  • Novartis Investigative Site

    Aachen, 52074

  • Novartis Investigative Site

    Augsburg, 86150

  • Novartis Investigative Site

    Berlin, 10117

  • Novartis Investigative Site

    Berlin, 10367

  • Novartis Investigative Site

    Berlin, 10713

  • Novartis Investigative Site

    Berlin, 10967

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Berlin, 13581

  • Novartis Investigative Site

    Berlin, 14195

  • Novartis Investigative Site

    Bielefeld, 33604

  • Novartis Investigative Site

    Böblingen, 71032

  • Novartis Investigative Site

    Bonn, 53111

  • Novartis Investigative Site

    Bottrop, 46236

  • Novartis Investigative Site

    Chemnitz, 09113

  • Novartis Investigative Site

    Cologne, 50935

  • Novartis Investigative Site

    Dessau, 06847

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Düsseldorf, 40225

  • Novartis Investigative Site

    Düsseldorf, 40479

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Essen, 45136

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Esslingen am Neckar, 73730

  • Novartis Investigative Site

    Frankfurt, 60398

  • Novartis Investigative Site

    Frankfurt, 60431

  • Novartis Investigative Site

    Freiburg im Breisgau, 79106

  • Novartis Investigative Site

    Fürstenwalde, 15517

  • Novartis Investigative Site

    Fürth, 90766

  • Novartis Investigative Site

    Georgsmarienhütte, 49124

  • Novartis Investigative Site

    Goslar, 38642

  • Novartis Investigative Site

    Göttingen, 37073

  • Novartis Investigative Site

    Greifswald, 17475

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Hamburg, 22081

  • Novartis Investigative Site

    Hamburg, 22767

  • Novartis Investigative Site

    Hanover, 30177

  • Novartis Investigative Site

    Hanover, 30559

  • Novartis Investigative Site

    Hanover, 30625

  • Novartis Investigative Site

    Heidelberg, 69115

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    Hildesheim, 31134

  • Novartis Investigative Site

    Homburg, 66421

  • Novartis Investigative Site

    Jena, 07740

  • Novartis Investigative Site

    Kiel, 24103

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Kulmbach, 95326

  • Novartis Investigative Site

    Landshut, 84028

  • Novartis Investigative Site

    Langen, Hesse, 63225

  • Novartis Investigative Site

    Leer, 26789

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Leipzig, 04277

  • Novartis Investigative Site

    Lübeck, Schleswig-Holstein, 23563

  • Novartis Investigative Site

    Mannheim, 68165

  • Novartis Investigative Site

    Marburg, 35037

  • Novartis Investigative Site

    Minden, 32429

  • Novartis Investigative Site

    Mönchengladbach, 41061

  • Novartis Investigative Site

    München, 80637

  • Novartis Investigative Site

    Munich, Bavaria, 80335

  • Novartis Investigative Site

    Münster, 48145

  • Novartis Investigative Site

    Münster, 48149

  • Novartis Investigative Site

    Neuruppin, 16816

  • Novartis Investigative Site

    Nuremberg, 90419

  • Novartis Investigative Site

    Offenbach, 63069

  • Novartis Investigative Site

    Oldenburg, 26121

  • Novartis Investigative Site

    Passau, 94032

  • Novartis Investigative Site

    Potsdam, 14467

  • Novartis Investigative Site

    Ravensburg, 88214

  • Novartis Investigative Site

    Recklinghausen, North Rhine-Westphalia, 45657

  • Novartis Investigative Site

    Rotenburg (Wümme), 27356

  • Novartis Investigative Site

    Saarbrücken, 66113

  • Novartis Investigative Site

    Schweinfurt, 97422

  • Novartis Investigative Site

    Stuttgart, 70199

  • Novartis Investigative Site

    Suhl, 98527

  • Novartis Investigative Site

    Torgau, 04860

  • Novartis Investigative Site

    Trier, 54290

  • Novartis Investigative Site

    Troisdorf, 53840

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Ulm, 89081

  • Novartis Investigative Site

    Velbert, 42551

  • Novartis Investigative Site

    Völklingen, 66333

  • Novartis Investigative Site

    Weinheim, 69469

  • Novartis Investigative Site

    Wetzlar, 35578

  • Novartis Investigative Site

    Wiesbaden, 65191

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

About this study

Official title: A National Phase IIIb, Multi-center, Open Label Study for Women and Men With Hormone-receptor Positive, HER-2 Negative Locally Advanced or Metastatic Breast Cancer Treated With Ribociclib (LEE011) in Combination With Letrozole

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.

Read the 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.

Being tested
ribociclib, letrozole, goserelin
Keywords
ribociclib, LEE011, RIBECCA, breast cancer, breast carcinoma, HR-positive, HER2-negative, advanced breast cancer, Letrozole, CDK4/6, breast lump, HER2 positive, metastatic breast cancer, breast cancer positive for human epidermal growth factor receptor 2 (HER2) HER2 positive metastatic breast cancer, breast cancer progression, estrogen-receptor (ER) positive(+) breast cancer, Paget's disease
Medical subject headings
Breast Neoplasms, Osteitis Deformans

What participants receive

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

  • ribociclibDrug

    Also called LEE011

    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.

  • 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.

  • goserelinDrug

    Premenopausal patients additionally received goserelin 3.6mg as monthly implant

Study groups in NCT03096847
Study groupRoleWhat they receive
ribociclib + letrozole cohort AExperimentalribociclib + letrozole cohort A - postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.
Receives: Drug: ribociclib; Drug: letrozole; Drug: goserelin
ribociclib + letrozole cohort B1Experimentalribociclib + 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
Receives: Drug: ribociclib; Drug: letrozole; Drug: goserelin
ribociclib + letrozole cohort B2Experimentalribociclib + 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
Receives: Drug: ribociclib; Drug: letrozole; Drug: goserelin

What is being measured

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

  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).

    Measured: At 24 weeks after last patient enrolled in trial

Secondary outcomes (10)

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

    PFS based on radiologic assessment by investigator using RECIST 1.1 criteria

    Measured: At week 24 , week 48 and week 72

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

    PFS based on radiologic assessment by investigator using RECIST 1.1 criteria

    Measured: Up to approximately month 25

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

    Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. For the Kaplan-Meier estimates (%, 95% CI), the probability of survival at week 24, 48 and 72 is reported below.

    Measured: At Week 24, Week 48 and Week 72

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

    Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.

    Measured: Up to approximatley 38 months

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

    Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.

    Measured: Up to approximatley 38 months

  6. Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI)

    Overall response rate (ORR) is the best overall response (BOR) of complete response (CR) or partial response (PR) as defined by RECIST 1.1.

    Measured: At week 24

  7. Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30

    The QLQ-C30 is the core questionnaire of the EORTC QLQ, which has been developed for the assessment of the health-related QOL of cancer patients participating in international clinical trials. Using a linear transformation to standardize the raw scores, all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher ("better") level of functioning (applies to the first 6 items, items 1 to 6), but a higher ("worse") level of symptoms (applies to the last 9 items, items 7 to 15). There is no aggregated total score, i.e., all scale scores were analyzed separately.

    Measured: Change from Baseline to Week 24

  8. Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7)

    To evaluate health related quality of life (QoL) via EORTC BR-23. The scoring approach for the QLQ-BR23 is identical in principle to that for the function and symptom scales / single items of the QLQ-C30, i.e., all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher ("better") level of functioning, (applies to the first 4 items, items 1 to 4) but a higher ("worse") level of symptoms (applies to the last 4 items, items 5 to 8).

    Measured: Baseline and Week 24 (Cycle 7)

  9. Time to 10% Deterioration in EORTC Global Health Status

    Time to 10% deterioration in the European Organisation for Research and Treatment of Cancer (EORTC) global health status

    Measured: up to approximately 10 months

  10. Number of Participants With Treatment Emergent Adverse Events (TEAE)

    Adverse Events (AEs) were separated into TEAEs (defined as AEs occurring/worsening from first study drug treatment until 30 days after the last study drug treatment) and AEs in the pre-/post-treatment period.

    Measured: Up to Week 72

Timeline

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

  1. First posted30 Mar 2017
  2. Study start24 Oct 2016
  3. Primary completion11 Dec 2018
  4. Study completion6 Feb 2020

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
502 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03096847
Sponsor's protocol ID
CLEE011XDE01
Other IDs
CLEE011XDE01, 2016-002556-24, 2016
Status last verified
Oct 2021
First submitted
10 Mar 2017
Last updated
11 Oct 2021
Data monitoring committee
No
FDA-regulated drug
No
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 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/.

Publications

  • 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.

    PubMed 34953442

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ribociclib, letrozole and goserelin in people with Advanced Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 84 sites in Germany.

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 8 inclusion and 10 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 11 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 84 sites in Germany. 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. 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 May 2021). 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?

Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole (time frame: At 24 weeks after last patient enrolled in trial). 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 NCT03096847, which also lists 1 linked publication.

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 11 Oct 2021.

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