Letrozole Plus Ribociclib or Placebo as Neo-adjuvant Therapy in ER-positive, HER2-negative Early Breast Cancer

Breast Cancer Clinical Trial

— FELINE  

Official title:

Femara (Letrozole) Plus Ribociclib (LEE011) or Placebo as Neo-adjuvant Endocrine Therapy for Women With ER-positive, HER2-negative Early Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02712723
• Other study ID #: CLEE011XUS10T
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: April 2023

Study information

• Verified date: September 2022
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if ribociclib in combination with letrozole for 24 weeks as neoadjuvant endocrine therapy increases the proportion of women with Pre-operative Endocrine Prognostic Index (PEPI) score of 0 at surgery compared to patients treated with letrozole alone therefore allowing more patients excellent outcomes without chemotherapy.

Description:

Subjects will be randomized (1:1:1) to either letrozole plus placebo vs. letrozole plus continuous dosing of ribociclib vs. letrozole plus intermittent dosing (3-weeks-on/1-week-off) of ribociclib.

The difference in clinical, pathologic and radiologic response as well as Pre-operative Endocrine Prognostic Index (PEPI) scores across the three treatments arms will be examined. Subjects will also be followed for 5 years post-treatment to determine if ribociclib in combination with letrozole for 24 weeks results in improved 5 year Relapse Free Survival (RFS) compared to letrozole alone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 121
• Est. completion date: April 2023
• Est. primary completion date: August 27, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Pathologically confirmed invasive breast cancer by core needle biopsy

• Female subjects, age = 18 years

• Only postmenopausal women will be eligible.

• Performance Status: Eastern Cooperative Oncology Group (ECOG) score 0-2

• Invasive breast cancer must be ER+ in =66 % of the cells or ER Allred score 6-8

• Invasive breast cancer must be HER2 negative.

• Clinical Stage II or III (by clinical measurement and/or breast imaging)

Key Exclusion Criteria:

• Subjects meeting any of the exclusion criteria at baseline will be excluded from study participation.

• Current use of other investigational agents

• Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema)

• An excisional biopsy of this breast cancer

• Surgical axillary staging procedure prior to study entry

• Hormone replacement therapy of any type, megestrol acetate, or raloxifene within four weeks prior to first study treatment

• Clinical or radiographic evidence of metastatic disease

• Clinically significant, uncontrolled heart disease

• Herbal preparations/medications as listed in Appendix B of the protocol

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Letrozole
Nonsteroidal aromatase inhibitor
• Ribociclib
Oral cyclin-dependent kinase (CDK) inhibitor
• Placebo
Placebo for ribociclib

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Miami Sylvester Comprehensive Cancer Center	Deerfield Beach	Florida
United States	City of Hope National Medical Center	Duarte	California
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center - South	Kansas City	Missouri
United States	University of Kansas Cancer Center - West	Kansas City	Kansas
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	University of Kansas Cancer Center - Overland Park	Overland Park	Kansas
United States	Cancer Research Collaboration	Santa Ana	California
United States	University of Kansas Cancer Center - Westwood	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Qamar Khan	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Pre-operative Endocrine Prognostic Index (PEPI) score 0 at surgery between ribociclib containing arms (combined) vs letrozole alone arm		At Surgery (22 weeks)
Secondary	Rate of complete cell cycle arrest at 2 weeks between ribociclib containing arms (combined) vs letrozole alone arm: Complete cell cycle arrest is defined as Ki67 at day 14 of < 2.7%		Day 14 of Cycle 1
Secondary	Pathologic complete response rate (pCR rate): pCR rate is defined as the proportion of patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes		At Surgery (Days 8-15 of Cycle 6)
Secondary	Clinical complete response rate (cCR rate): cCR rate is defined as the proportion of patients with no residual tumor by clinical exam		Post-surgery (Once in the first 4 weeks of post-op, then once every 6 months for 5 years post-op)
Secondary	5 Year Relapse Free Survival (RFS)		5 years post-treatment