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Breast CancerPhase 3EarLEE-2NCT03081234

Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- Intermediate Risk Early Breast Cancer

A Phase 3 study testing Ribociclib and Adjuvant endocrine therapy in people with Breast Cancer, run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an international, multi-center, randomized, double-blinded, placebo-controlled clinical study evaluating the efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, intermediate risk breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Ribociclib and Adjuvant endocrine therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
31 Mar 2018to 17 Nov 2025
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Histologically confirmed unilateral primary invasive adenocarcinoma of the breast
  • Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
  • Patient is after surgical resection of the tumor where tumor was removed completely with surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen
  • Patient who have AJCC 8th edition Prognostic Stage Group II
  • Patient has completed adjuvant radiotherapy (if indicated) according to the institutional guidelines prior to screening
  • Patient may already have initiated adjuvant endocrine therapy (ET) at the time of randomization, but randomization must take place within 52 weeks of date of initial histological diagnosis of breast cancer and within 12 weeks of initiating ET
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  • ECOG Performance Status 0 or 1
  • Adequate bone marrow and organ function
  • Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within normal limits
  • QTcF interval < 450 msec and mean resting heart rate 50-90 bpm

Who cannot join

  • Prior neoadjuvant therapy (endocrine therapy or chemotherapy) or CDK4/6 inhibitor
  • Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last 2 years
  • Patient with inflammatory breast cancer
  • Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin or 900 mg/m² or more for epirubicin
  • Distant metastases of breast cancer beyond regional lymph nodes
  • Patient has not recovered from clinical and laboratory acute toxicities of chemotherapy, radiotherapy and surgery
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  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmias
  • Uncontrolled hypertension with systolic blood pressure >160 mmHg
  • Patient is currently receiving any of the prohibited substances that cannot be discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5; medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment; concomitant medications with a known risk to prolong the QT interval and/or known to cause torsades de points that cannot be discontinued or replaced by safe alternative medication.
  • Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the study
  • Women of child-bearing potential unless they are using highly effective methods of contraception during the study treatment and for 21 days after stopping the study treatment.

About this study

Official title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, Intermediate Risk Early Breast Cancer

This is an international, multi-center, randomized, double-blinded, placebo-controlled clinical study evaluating the efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, intermediate risk breast cancer.

Read the detailed description

While adjuvant endocrine therapy (ET) is effective in reducing risk of recurrence in patients with hormone receptor (HR)-positive early breast cancer (EBC), recurrences are still common, especially in patients with unfavorable clinical, pathological and/or molecular features. Ribociclib, a CDK4/6 inhibitor, demonstrated clinical efficacy with tolerable toxicity when added to ET in patients with HR-positive, HER2-negative advanced breast cancer. The purpose of this study is to evaluate the effect of addition of ribociclib to standard adjuvant ET on invasive disease-free survival in patients with HR+, HER2- intermediate-risk EBC.

Conditions
Breast Cancer
Being tested
Ribociclib, Placebo, Adjuvant endocrine therapy
Keywords
Hormone receptor-positive, Estrogen and/or progesterone receptor-positive, HER2-negative, Intermediate risk early breast cancer, Adjuvant, Ribociclib, LEE011, CDK4/6 inhibitor, Endocrine therapy, Phase III, breast carcinoma, breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

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

  • RibociclibDrug

    Also called LEE011

    Ribociclib 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Ribociclib will be supplied in the form of 200 mg tablets.

  • PlaceboDrug

    Placebo 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Placebo will be supplied in the form of 200 mg tablets.

  • Adjuvant endocrine therapyDrug

    Tamoxifen 20 mg daily, or letrozole 2.5 mg daily, or anastrozole 1 mg daily, or exemestane 25 mg daily (male patients will be treated with tamoxifen 20 mg daily) for a total duration of at least 60 months. In premenopausal women, adjuvant endocrine therapy may include GnRH agonist administered every 28 days.

Study groups in NCT03081234
Study groupRoleWhat they receive
Ribociclib + adjuvant endocrine therapyExperimentalRibociclib in combination with standard adjuvant endocrine therapy
Receives: Drug: Ribociclib; Drug: Adjuvant endocrine therapy
Placebo + adjuvant endocrine therapyActive comparatorPlacebo in combination with standard adjuvant endocrine therapy
Receives: Drug: Placebo; Drug: Adjuvant endocrine therapy

What is being measured

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

  1. Invasive disease-free survival (iDFS) using STEEP criteria

    iDFS is defined as the time from the date of randomization to the date of the first event of local invasive breast recurrence, regional invasive recurrence, distant recurrence, death, contralateral invasive breast cancer, or second primary non-breast invasive cancer, and is assessed locally by investigators.

    Measured: up to 90 months

Secondary outcomes (4)

  1. Recurrence-free survival (RFS) using STEEP criteria

    RFS is defined as the time from date of randomization to date of first event of local invasive breast recurrence, regional invasive recurrence, distant recurrence, or death.

    Measured: up to 90 months

  2. Distant disease-free survival (DDFS) using STEEP criteria

    DDFS is defined as the time from date of randomization to date of first event of distant recurrence, death, or second primary non-breast invasive cancer

    Measured: up to 90 months

  3. Overall survival (OS)

    OS is defined as the time from date of randomization to date of death due to any cause.

    Measured: up to 90 months

  4. Quality of Life (QOL)

    Change from baseline in the physical functioning sub-scale score and global health status/QOL scale score as assessed by EORTC QLQ-C30

    Measured: Baseline, 90 months

Timeline

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

  1. First posted16 Mar 2017
  2. Study start31 Mar 2018 (estimated)
  3. Primary completion17 Nov 2025 (estimated)
  4. Study completion17 Nov 2025 (estimated)

Why it stopped: Withdrawn due to change in plan for this study and not due to safety reasons.

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03081234
Sponsor's protocol ID
CLEE011H2301
Acronym
EarLEE-2
Status last verified
Mar 2018
First submitted
1 Mar 2017
Last updated
15 Mar 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: 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 trials in line with applicable laws and regulations. This trial data will be available according to the process described on www.clinicalstudydatarequest.com.

Publications

  • Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007 May 20;25(15):2127-32. doi: 10.1200/JCO.2006.10.3523.

    PubMed 17513820

  • Hortobagyi GN, Connolly JL, D'Orsi CJ, et al (2017). Breast. From AJCC Cancer Staging Manual 8th ed. By Amin MB, Edge S, Greene FL, et al. Springer

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ribociclib and Adjuvant endocrine therapy in people with Breast Cancer, run by Novartis Pharmaceuticals.

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 10 inclusion and 11 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: withdrawn, as of the sponsor's last update on 15 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Invasive disease-free survival (iDFS) using STEEP criteria (time frame: up to 90 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 NCT03081234, which also lists 2 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 15 Mar 2018; AzTrials last refreshed its copy on 6 Nov 2026.

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