NCT02712723

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
121

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline
7mo left

Started Feb 2016

Longer than P75 for phase_2 breast-cancer

Geographic Reach
1 country

13 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress95%
Feb 2016Dec 2026

Study Start

First participant enrolled

February 1, 2016

Completed
24 days until next milestone

First Submitted

Initial submission to the registry

February 25, 2016

Completed
22 days until next milestone

First Posted

Study publicly available on registry

March 18, 2016

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 27, 2018

Completed
7.5 years until next milestone

Results Posted

Study results publicly available

March 11, 2026

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Expected
Last Updated

March 11, 2026

Status Verified

February 1, 2026

Enrollment Period

2.6 years

First QC Date

February 25, 2016

Results QC Date

November 28, 2025

Last Update Submit

February 18, 2026

Conditions

Breast Cancer

Keywords

ER+, HER2-negative breast cancerStage II or IIILetrozoleFemaraRibociclibLEE011Neo-adjuvant

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Rate of Complete Cell Cycle Arrest at 2 Weeks Between Ribociclib Containing Arms (Combined) vs Letrozole Alone Arm.

    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

    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)

  • 5 Year Relapse Free Survival (RFS)

    5 years post-treatment

Study Arms (3)

Placebo + Letrozole

ACTIVE COMPARATOR

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

Drug: LetrozoleDrug: Placebo

Ribociclib 600 mg + Letrozole

EXPERIMENTAL

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

Drug: LetrozoleDrug: Ribociclib

Ribociclib 400 mg + Letrozole

EXPERIMENTAL

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

Drug: LetrozoleDrug: Ribociclib

Interventions

LetrozoleDRUG

Nonsteroidal aromatase inhibitor

Also known as: Femara, CGS 20267, LTZ
Placebo + LetrozoleRibociclib 400 mg + LetrozoleRibociclib 600 mg + Letrozole
RibociclibDRUG

Oral cyclin-dependent kinase (CDK) inhibitor

Also known as: LEE011, LEE-011
Ribociclib 400 mg + LetrozoleRibociclib 600 mg + Letrozole
PlaceboDRUG

Placebo for ribociclib

Placebo + Letrozole

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Cancer Research Collaboration

Santa Ana, California, 92705, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Deerfield Beach, Florida, 33442, United States

Location

University of Kansas Cancer Center - West

Kansas City, Kansas, 66112, United States

Location

University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, 66210, United States

Location

University of Kansas Cancer Center - Westwood

Westwood, Kansas, 66205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Kansas Cancer Center - South

Kansas City, Missouri, 64131, United States

Location

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozoleribociclib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

NitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Qamar Khan
Organization
UKansasMCRI
qkhan@kumc.edu
9137106387

Study Officials

  • Qamar Khan, MD

    University of Kansas Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

February 25, 2016

First Posted

March 18, 2016

Study Start

February 1, 2016

Primary Completion

August 27, 2018

Study Completion (Estimated)

December 1, 2026

Last Updated

March 11, 2026

Results First Posted

March 11, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

US(13)