Clinical Trials /

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

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:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Letrozole</span> Plus <span class="go-doc-concept go-doc-intervention">Ribociclib</span> or <span class="go-doc-concept go-doc-intervention">Placebo</span> as Neo-adjuvant Therapy in ER-positive, <span class="go-doc-concept go-doc-biomarker">HER2</span>-negative Early Breast Cancer

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

    NCT ID: NCT02712723

    ORG ID: CLEE011XUS10T

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Letrozole Femara, CGS 20267, LTZ Placebo + Letrozole, Ribociclib 600 mg + Letrozole, Ribociclib 400 mg + Letrozole
    Ribociclib LEE011, LEE-011 Ribociclib 600 mg + Letrozole, Ribociclib 400 mg + Letrozole
    Placebo Placebo + Letrozole

    Trial 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.

    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

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    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)

    Trial Keywords

    ER+, HER2-negative breast cancer

    Stage II or III

    Letrozole

    Femara

    Ribociclib

    LEE011

    Neo-adjuvant