Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer (EarLEE-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03078751
Recruitment Status : Completed
First Posted : March 13, 2017
Results First Posted : January 15, 2021
Last Update Posted : October 11, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This was an open label, multi-center protocol for U.S. patients enrolled in the study of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, high risk early breast cancer

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Ribociclib Drug: Adjuvant endocrine therapy Drug: Placebo Phase 2

Detailed Description:

The purpose of this study was to evaluate the preliminary safety and tolerability of ribociclib to standard adjuvant endocrine therapy (ET) in patients with hormone receptor (HR) positive, Human Epidermal Growth Factor Receptor2 (HER2) negative high risk early breast cancer (EBC).

Originally, this was a randomized, Phase III, double-blind, placebo-controlled, multi-center, international study to evaluate efficacy and safety of ribociclib with ET as an adjuvant treatment in patients with HR-positive, HER2-negative, high risk EBC.

Patients were randomized at a ratio of 1:1 to receive either ribociclib or placebo for approximately 24 months in combination with a standard adjuvant ET with ET continued for at least 60 months.

However, following a review of the ribociclib development program strategy, a decision was taken to explore a different approach by initiating a single Phase III study for simplicity of trial logistics and for the purpose of analyzing the overall population through a single clinical trial. Therefore, this study was closed to enrollment early and was amended to be an open label, multi-center Phase II study conducted in the US only. All randomized patients were unblinded; patients randomized to placebo were permanently discontinued from the study and patients randomized to ribociclib were offered the option to continue treatment with ribociclib + ET.

The study included a screening phase (28 days), a treatment phase composed of maximum of 26 cycles of ribociclib in combination with ET (approximately 24 months) or until disease recurrence, intolerable toxicity, withdrawal of consent, or discontinuation from the study treatment for any other reason, whichever was earlier, and a 30 days safety follow up from last dose of ribociclib. Ribociclib was given orally once a day on days 1 to 21 in each 28 days cycle.

Safety was assessed for each patient until 30 days after the last dose of ribociclib and included routine safety monitoring except in case of death, loss to follow up or withdrawal of consent.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: The trial used to be a placebo-controlled, blinded trial. It was amended to an open-label trial after protocol amendment 2.
Primary Purpose: Treatment
Official Title: An Open Label, Multi-center Protocol for U.S. Patients Enrolled in a Study of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, High Risk Early Breast Cancer
Actual Study Start Date : June 20, 2017
Actual Primary Completion Date : March 9, 2020
Actual Study Completion Date : March 9, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ribociclib

Arm Intervention/treatment
Experimental: Ribociclib + adjuvant endocrine therapy (ET)

Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy.

ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)

Drug: Ribociclib

Ribociclib 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months).

Ribociclib was supplied in the form of 200 mg film-coated tablets taken by mouth.

Other Name: LEE011

Drug: Adjuvant endocrine therapy
Letrozole 2.5 mg by mouth daily, or anastrozole 1 mg by mouth daily, exemestane 25 mg by mouth daily, tamoxifen 20 mg by mouth daily, for a total duration of at least 60 months. In premenopausal women, a GnRH agonist administered every 28 days.

Placebo Comparator: Placebo + adjuvant endocrine therapy (ET)
Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
Drug: Adjuvant endocrine therapy
Letrozole 2.5 mg by mouth daily, or anastrozole 1 mg by mouth daily, exemestane 25 mg by mouth daily, tamoxifen 20 mg by mouth daily, for a total duration of at least 60 months. In premenopausal women, a GnRH agonist administered every 28 days.

Drug: Placebo

Placebo 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months).

Placebo was supplied in the form of 200 mg film-coated tablets taken by mouth.





Primary Outcome Measures :
  1. Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Up to 26 months ]
    These are the number of participants who had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not

  2. Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Up to 26 months ]
    These are the percentage of participants that had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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 the final surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen
  • Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage Group III tumor; or patient who received neoadjuvant chemotherapy and have 1 or more ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue
  • Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles or ≥ 12 weeks which included taxanes prior to screening
  • Patient has completed adjuvant radiotherapy (if indicated) 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
  • 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

Key Exclusion Criteria:

  • Prior treatment with 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
  • 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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03078751


Locations
Show Show 33 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] April 17, 2018
Statistical Analysis Plan  [PDF] February 24, 2020

Additional Information:
Publications of Results:
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03078751    
Other Study ID Numbers: CLEE011G2301
2014-001795-53 ( EudraCT Number )
First Posted: March 13, 2017    Key Record Dates
Results First Posted: January 15, 2021
Last Update Posted: October 11, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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 triasl in line with applicable laws and regulations.

This trial data will be available according to the process described on www.clinicalstudydatarequest.com.


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Hormone receptor-positive
Estrogen and/or progesterone receptor-positive
HER2-negative
High risk early breast cancer
Adjuvant
Ribociclib
LEE011
CDK4/6 inhibitor
Endocrine therapy
Phase II
Breast carcinoma
Breast cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases