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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Letrozole; Drug: Placebo; Drug: Ribociclib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Santa Ana, California, United States, 92705
      • Cancer Research Collaboration
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami Sylvester Comprehensive Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66112
      • University of Kansas Cancer Center - West
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center - Overland Park
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center - Westwood
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • University of Kansas Cancer Center - North
    • Kansas City, Missouri, United States, 64131
      • University of Kansas Cancer Center - South
    • Lee's Summit, Missouri, United States, 64064
      • University of Kansas Cancer Center - Lee's Summit
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo + Letrozole; Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily	Drug: Letrozole; Nonsteroidal aromatase inhibitor; Other Names: CGS 20267; Femara; LTZ; Drug: Placebo; Placebo for ribociclib
Experimental: Ribociclib 600 mg + Letrozole; Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily	Drug: Letrozole; Nonsteroidal aromatase inhibitor; Other Names: CGS 20267; Femara; LTZ; Drug: Ribociclib; Oral cyclin-dependent kinase (CDK) inhibitor; Other Names: LEE011; LEE-011
Experimental: Ribociclib 400 mg + Letrozole; Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily	Drug: Letrozole; Nonsteroidal aromatase inhibitor; Other Names: CGS 20267; Femara; LTZ; Drug: Ribociclib; Oral cyclin-dependent kinase (CDK) inhibitor; Other Names: LEE011; LEE-011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm.	The Preoperative Endocrine Prognostic Index (PEPI) score 0 is defined as: pT stage 0, 1, or 2 at surgery after 24 weeks of neoadjuvant therapy; negative axillary lymph nodes at surgey; Ki67 of ≤ 2.7 % at surgery; and tumor is ER+ at surgery. A PEPI score of 0 predicts a good outcome compare to PEPI score >0.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5 Year Relapse Free Survival (RFS)		5 years post-treatment
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
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	pCR is assciated with better outcomes in breast cancer	At Surgery (Days 8-15 of Cycle 6)
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)

Collaborators and Investigators

• Sponsor: Qamar Khan
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Qamar Khan, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): August 27, 2018
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 25, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimated): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Ribociclib; LEE011; Letrozole; Neo-adjuvant; Femara; ER+, HER2-negative breast cancer; Stage II or III
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nitriles; Triazoles; Letrozole; ribociclib
• Other Study ID Numbers: CLEE011XUS10T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO