Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

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)

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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:
    • Femara
    • CGS 20267
    • 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:
    • Femara
    • CGS 20267
    • 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:
    • Femara
    • CGS 20267
    • LTZ
  • Drug: Ribociclib
    Oral cyclin-dependent kinase (CDK) inhibitor
    Other names:
    • LEE011
    • LEE-011

Recruiting Locations

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Issam Makhoul, MD

City of Hope National Medical Center
Duarte, California 91010
Contact:
Yuan Yuan, MD

University of Miami Sylvester Comprehensive Cancer Center
Deerfield Beach, Florida 33442
Contact:
Mohammad Jahanzeb, MD

University of Kansas Cancer Center - West
Kansas City, Kansas 66112
Contact:
913-945-7552
ctnursenav@kumc.edu

University of Kansas Cancer Center - Overland Park
Overland Park, Kansas 66210
Contact:
913-945-7552
ctnursenav@kumc.edu

University of Kansas Cancer Center - Westwood
Westwood, Kansas 66205
Contact:
913-945-7552
ctnursenav@kumc.edu

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Aditya Bardia, MD

University of Kansas Cancer Center - South
Kansas City, Missouri 64131
Contact:
913-945-7552
ctnursenav@kumc.edu

University of Kansas Cancer Center - North
Kansas City, Missouri 64154
Contact:
913-945-7552
ctnursenav@kumc.edu

University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
Contact:
913-945-7552
ctnursenav@kumc.edu

Columbia University Medical Center
New York, New York 10032
Contact:
Meghna Trivedi, MD

University of Wisconsin Carbone Cancer Center
Madison, Wisconsin 53705
Contact:
Kari Wisinski, MD

More Details

NCT ID
NCT02712723
Status
Recruiting
Sponsor
Qamar Khan

Study Contact

Clinical Trials Nurse Navigator
913-945-7552
ctnursenav@kumc.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.