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

NCT ID: NCT03078751

Last Updated: 2021-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-20
• Study Completion Date: 2020-03-09

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

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Ribociclib

Intervention Type: DRUG

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.

Adjuvant endocrine therapy

Intervention Type: DRUG

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 + 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

Group Type: PLACEBO_COMPARATOR

Adjuvant endocrine therapy

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

LEE011

Eligibility Criteria

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

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.

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

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Arizona Oncology Associates PC- HAL

Tucson, Arizona, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

CBCC Global Research

Bakersfield, California, United States

University of California - Los Angeles

Los Angeles, California, United States

Ventura County Hematology and Oncology

Oxnard, California, United States

TRIO - Torrance Health Association

Redondo Beach, California, United States

Innovative Clinical Research Institute

Whittier, California, United States

Rocky Mountain Cancer Centers Regulatory

Denver, Colorado, United States

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, United States

Florida Cancer Specialists South Region

Fort Myers, Florida, United States

Memorial Regional Hospital

Hollywood, Florida, United States

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Florida Cancer Specialists - North Florida Cancer Specialist N

St. Petersburg, Florida, United States

Northside Hospital Central Research Dept.

Atlanta, Georgia, United States

Summit Cancer Care, PC

Savannah, Georgia, United States

Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Div.

Leawood, Kansas, United States

Maryland Oncology Hematology P A

Silver Spring, Maryland, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Saint Barnabas Medical Center 2nd Floor East Wing

Livingston, New Jersey, United States

Pro Health Care Associates

New Hyde Park, New York, United States

The Presbyterian Hospital

Charlotte, North Carolina, United States

Tennessee Oncology, PLLC

Chattanooga, Tennessee, United States

The West Clinic

Germantown, Tennessee, United States

SCRI - Tennessee Oncology

Nashville, Tennessee, United States

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology P A Texas Oncology - Houston

Dallas, Texas, United States

Millennium Oncology

Houston, Texas, United States

Cancer Care Network of South Texas

San Antonio, Texas, United States

Texas Oncology PA - Tyler

Tyler, Texas, United States

Fairfax Northern Virginia Hem/Onc

Fairfax, Virginia, United States

Multicare Institute for Research and Innovation

Tacoma, Washington, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 17513820 (View on PubMed)

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

Reference Type: RESULT

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=724

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

2014-001795-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLEE011G2301

Identifier Type: -

Identifier Source: org_study_id