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

Primary Purpose

Breast Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Letrozole
Ribociclib
Placebo
Sponsored by
Qamar Khan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring ER+, HER2-negative breast cancer, Stage II or III, Letrozole, Femara, Ribociclib, LEE011, Neo-adjuvant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas for Medical Sciences
  • City of Hope National Medical Center
  • Cancer Research Collaboration
  • University of Miami Sylvester Comprehensive Cancer Center
  • University of Kansas Cancer Center - West
  • University of Kansas Cancer Center - Overland Park
  • University of Kansas Cancer Center - Westwood
  • Massachusetts General Hospital
  • University of Kansas Cancer Center - South
  • University of Kansas Cancer Center - North
  • University of Kansas Cancer Center - Lee's Summit
  • Columbia University Medical Center
  • University of Wisconsin Carbone Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Placebo + Letrozole

Ribociclib 600 mg + Letrozole

Ribociclib 400 mg + Letrozole

Arm Description

Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily

Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily

Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily

Outcomes

Primary Outcome Measures

Rate of Pre-operative Endocrine Prognostic Index (PEPI) score 0 at surgery between ribociclib containing arms (combined) vs letrozole alone arm

Secondary Outcome Measures

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%
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
Clinical complete response rate (cCR rate): cCR rate is defined as the proportion of patients with no residual tumor by clinical exam
5 Year Relapse Free Survival (RFS)

Full Information

First Posted
February 25, 2016
Last Updated
September 24, 2022
Sponsor
Qamar Khan
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02712723
Brief Title
Letrozole Plus Ribociclib or Placebo as Neo-adjuvant Therapy in ER-positive, HER2-negative Early Breast Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2016 (Actual)
Primary Completion Date
August 27, 2018 (Actual)
Study Completion Date
April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Qamar Khan
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
ER+, HER2-negative breast cancer, Stage II or III, Letrozole, Femara, Ribociclib, LEE011, Neo-adjuvant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
121 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo + Letrozole
Arm Type
Active Comparator
Arm Description
Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily
Arm Title
Ribociclib 600 mg + Letrozole
Arm Type
Experimental
Arm Description
Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily
Arm Title
Ribociclib 400 mg + Letrozole
Arm Type
Experimental
Arm Description
Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Femara, CGS 20267, LTZ
Intervention Description
Nonsteroidal aromatase inhibitor
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Other Intervention Name(s)
LEE011, LEE-011
Intervention Description
Oral cyclin-dependent kinase (CDK) inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for ribociclib
Primary Outcome Measure Information:
Title
Rate of Pre-operative Endocrine Prognostic Index (PEPI) score 0 at surgery between ribociclib containing arms (combined) vs letrozole alone arm
Time Frame
At Surgery (22 weeks)
Secondary Outcome Measure Information:
Title
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%
Time Frame
Day 14 of Cycle 1
Title
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
Time Frame
At Surgery (Days 8-15 of Cycle 6)
Title
Clinical complete response rate (cCR rate): cCR rate is defined as the proportion of patients with no residual tumor by clinical exam
Time Frame
Post-surgery (Once in the first 4 weeks of post-op, then once every 6 months for 5 years post-op)
Title
5 Year Relapse Free Survival (RFS)
Time Frame
5 years post-treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qamar Khan, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Cancer Research Collaboration
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33442
Country
United States
Facility Name
University of Kansas Cancer Center - West
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66112
Country
United States
Facility Name
University of Kansas Cancer Center - Overland Park
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
University of Kansas Cancer Center - Westwood
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Kansas Cancer Center - South
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
University of Kansas Cancer Center - North
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64154
Country
United States
Facility Name
University of Kansas Cancer Center - Lee's Summit
City
Lee's Summit
State/Province
Missouri
ZIP/Postal Code
64064
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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