Clinical Trial: NCT02712723 - My Cancer Genome

NCT02712723

Description:

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.

Related Conditions:

Breast Carcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02712723

Trial Eligibility

Document

Title

Brief Title: 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

Clinical Trial IDs

ORG STUDY ID: CLEE011XUS10T
NCT ID: NCT02712723

Conditions

Breast Cancer

Interventions

Drug	Synonyms	Arms
Letrozole	Femara, CGS 20267, LTZ	Placebo + Letrozole
Ribociclib	LEE011, LEE-011	Ribociclib 400 mg + Letrozole
Placebo		Placebo + Letrozole

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
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	Letrozole Placebo
Ribociclib 600 mg + Letrozole	Experimental	Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily	Letrozole Ribociclib
Ribociclib 400 mg + Letrozole	Experimental	Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily	Letrozole Ribociclib

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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Female
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	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)
Safety Issue:
Description:

Secondary Outcome Measures

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%
Time Frame:	Day 14 of Cycle 1
Safety Issue:
Description:

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
Time Frame:	At Surgery (Days 8-15 of Cycle 6)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	5 Year Relapse Free Survival (RFS)
Time Frame:	5 years post-treatment
Safety Issue:
Description:

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Qamar Khan

Trial Keywords

ER+, HER2-negative breast cancer
Stage II or III
Letrozole
Femara
Ribociclib
LEE011
Neo-adjuvant

Last Updated

August 29, 2019

Clinical Trials /

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