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

Breast Cancer Clinical Trial

— EarLEE-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03078751
• Other study ID #: CLEE011G2301
• Secondary ID: 2014-001795-53
• Status: Completed
• Phase: Phase 2
• Start date: June 20, 2017
• Est. completion date: March 9, 2020

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.
• 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
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.

Locations

Country	Name	City	State
United States	Northside Hospital Central Research Dept.	Atlanta	Georgia
United States	CBCC Global Research	Bakersfield	California
United States	The Presbyterian Hospital	Charlotte	North Carolina
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology P A Texas Oncology - Houston	Dallas	Texas
United States	Rocky Mountain Cancer Centers Regulatory	Denver	Colorado
United States	Fairfax Northern Virginia Hem/Onc	Fairfax	Virginia
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Florida Cancer Specialists South Region	Fort Myers	Florida
United States	The West Clinic	Germantown	Tennessee
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Millennium Oncology	Houston	Texas
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Div.	Leawood	Kansas
United States	Saint Barnabas Medical Center 2nd Floor East Wing	Livingston	New Jersey
United States	University of California - Los Angeles	Los Angeles	California
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Pro Health Care Associates	New Hyde Park	New York
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Ventura County Hematology and Oncology	Oxnard	California
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	TRIO - Torrance Health Association	Redondo Beach	California
United States	Florida Cancer Specialists - North Florida Cancer Specialist N	Saint Petersburg	Florida
United States	Cancer Care Network of South Texas	San Antonio	Texas
United States	Summit Cancer Care, PC	Savannah	Georgia
United States	Maryland Oncology Hematology P A	Silver Spring	Maryland
United States	Multicare Institute for Research and Innovation	Tacoma	Washington
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Arizona Oncology Associates PC- HAL	Tucson	Arizona
United States	Texas Oncology PA - Tyler	Tyler	Texas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (2)

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

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 Onco — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events and Serious Adverse Events	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	Up to 26 months
Primary	Percentage of Participants With Adverse Events and Serious Adverse Events	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	Up to 26 months

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com