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

This study is currently recruiting participants.
Verified November 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT03078751
First Posted: March 13, 2017
Last Update Posted: November 8, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
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, high risk breast cancer.

Condition Intervention Phase
Breast Cancer Drug: Ribociclib Drug: Placebo Drug: Adjuvant endocrine therapy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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, High Risk Early Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Invasive disease-free survival (iDFS) using STEEP criteria [ Time Frame: Up to 54 months ]
    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.


Secondary Outcome Measures:
  • Recurrence-free survival (RFS) using STEEP criteria [ Time Frame: up to 77 months ]
    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.

  • Distant disease-free survival (DDFS) using STEEP criteria [ Time Frame: up to 77 months ]
    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

  • Overall survival (OS) [ Time Frame: up to 77 months ]
    OS is defined as the time from date of randomization to date of death due to any cause.

  • Quality of Life (QoL) [ Time Frame: Baseline, 77 months ]
    Change from baseline in the physical functioning sub-scale score and the global health status/QOL scale score as assessed by EORTC QLQ-C30


Estimated Enrollment: 2000
Actual Study Start Date: June 20, 2017
Estimated Study Completion Date: September 13, 2023
Estimated Primary Completion Date: September 13, 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ribociclib + adjuvant endocrine therapy
Ribociclib in combination with standard adjuvant endocrine therapy
Drug: Ribociclib

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.

Other Name: LEE011
Drug: Adjuvant endocrine therapy
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 will include GnRH agonist administered every 28 days.
Active Comparator: Placebo + adjuvant endocrine therapy
Placebo in combination with standard adjuvant endocrine therapy
Drug: Placebo

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.

Drug: Adjuvant endocrine therapy
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 will include GnRH agonist administered every 28 days.

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- high-risk EBC.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  Contacts and Locations
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


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

  Show 66 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03078751     History of Changes
Other Study ID Numbers: CLEE011G2301
2014-001795-53 ( EudraCT Number )
First Submitted: February 27, 2017
First Posted: March 13, 2017
Last Update Posted: November 8, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.


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 III
Breast carcinoma
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs