Femara (Letrozole) Plus Ribociclib (LEE011) or Placebo as Neo-adjuvant Endocrine Therapy for Women With ER-positive, HER2-negative Early Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 121
- 试验地点
- 13
- 主要终点
- Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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
干预措施: Placebo (Drug)
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
干预措施: Letrozole (Drug)
Ribociclib 400 mg + Letrozole
Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily
干预措施: Letrozole (Drug)
Ribociclib 600 mg + Letrozole
Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily
干预措施: Letrozole (Drug)
Ribociclib 600 mg + Letrozole
Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily
干预措施: Ribociclib (Drug)
Ribociclib 400 mg + Letrozole
Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily
干预措施: Ribociclib (Drug)
结局指标
主要结局
Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm.
时间窗: 24 weeks
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.
次要结局
- 5 Year Relapse Free Survival (RFS)(5 years post-treatment)
- 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))
研究者
Qamar Khan
Associate Professor
University of Kansas Medical Center