Clinical trial NCT02712723: Letrozole Plus Ribociclib or Placebo as Neo-adjuvant Therapy in ER-positive, HER2-negative Early Breast Cancer
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: ER+, HER2-negative breast cancer
Stage II or III
Letrozole
Femara
Ribociclib
LEE011
Neo-adjuvant
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2016-03-18
Enrollment: 121
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of Pre-operative Endocrine Prognostic Index (PEPI) score 0 at surgery between ribociclib containing arms (combined) vs letrozole alone arm
timeFrame: At Surgery (22 weeks)
Secondary outcomes:
measure: 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%
timeFrame: Day 14 of Cycle 1
measure: 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
timeFrame: At Surgery (Days 8-15 of Cycle 6)
measure: Clinical complete response rate (cCR rate): cCR rate is defined as the proportion of patients with no residual tumor by clinical exam
timeFrame: Post-surgery (Once in the first 4 weeks of post-op, then once every 6 months for 5 years post-op)
measure: 5 Year Relapse Free Survival (RFS)
timeFrame: 5 years post-treatment
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Santa Ana
country: United States
facility: Cancer Research Collaboration
state: California
city: Deerfield Beach
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - West
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center - Overland Park
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center - Westwood
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - South
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - North
state: Missouri
city: Lee's Summit
country: United States
facility: University of Kansas Cancer Center - Lee's Summit
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Kansas Medical Center
name: Qamar Khan, MD
role: PRINCIPAL_INVESTIGATOR
References: