A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Nonsteroidal Aromatase Inhibitors (Anastrozole or Letrozole) Plus LY2835219, a CDK4/6 Inhibitor, or Placebo in Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer With No Prior Systemic Therapy in This Disease Setting
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 493
- 试验地点
- 155
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The main purpose of this study is to evaluate how effective nonsteroidal aromatase inhibitors (NSAI) plus abemaciclib are in postmenopausal women with breast cancer. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio.
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
- Double (Participant, Care Provider)
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
- •Have a diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer
- •Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease
- •Have postmenopausal status
- •Have either measurable disease or nonmeasurable bone-only disease
- •Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have adequate organ function
- •Have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture prior to randomization and recovered from the acute effects of therapy
- •Are able to swallow capsules
排除标准
- •Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis
- •Have inflammatory breast cancer
- •Have clinical evidence or a history of central nervous system (CNS) metastasis
- •Are currently receiving or have previously received endocrine therapy for locoregionally recurrent or metastatic breast cancer
- •Have received prior (neo)adjuvant endocrine therapy with a disease-free interval ≤12 months from completion of treatment
- •Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer
- •Have received prior treatment with everolimus
- •Have received prior treatment with any cyclin-dependent kinase (CDK) 4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)
- •Have initiated bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents <7 days prior to randomization
- •Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively
- •Have had major surgery within 14 days prior to randomization
研究组 & 干预措施
Abemaciclib + NSAI
150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
干预措施: Letrozole (Drug)
Abemaciclib + NSAI
150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
干预措施: Abemaciclib (Drug)
Abemaciclib + NSAI
150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
干预措施: Anastrozole (Drug)
Placebo + NSAI
Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
干预措施: Anastrozole (Drug)
Placebo + NSAI
Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
干预措施: Letrozole (Drug)
Placebo + NSAI
Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
PFS defined as the time from the first day of therapy to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
次要结局
- PK: Hepatic Clearance of Abemaciclib, and Apparent Hepatic Clearance of Its Metabolites M2 and M20(Cycle 1 Day 1; 2 to 4 hours (h) post dose, Cycle 2 Day 1; 3 h post dose; 7 h post dose, Cycle 3 Day 1; pre dose, 3 h post dose)
- Overall Survival (OS)(Randomization to Progressive Disease or Death Due to Any Cause (Estimated Up to 82 Months))
- Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])(Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months))
- Duration of Response (DoR)(CR or PR to Disease Progression or Death Due to Any Cause (Up to 32 Months))
- Percentage of Participants With CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])(Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months))
- Percentage of Participants With Tumor Response of SD for at Least 6 Months, PR, or CR (Clinical Benefit Rate [CBR])(Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months))
- Change From Baseline to End of Study in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional Scale Scores(Baseline, End of Study (Up to 32 Months))
- Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-C30 Symptom Scale Scores(Baseline, End of Study (Up to 32 Months))
- Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-Breast23 Questionnaire(Baseline, End of Study (Up to 32 Months))
- Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L) Index Value(Baseline, End of Study (Up to 32 Months))
- Change From Baseline to End of Study in Health Status on the EuroQol-5D 5L Visual Analog Scale (VAS) Scores Scale(Baseline, End of Study (Up to 32 Months))
- Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity [AUC(0-∞)] of Abemaciclib and Its Metabolites M2 and M20(Cycle 1 Day 1; 2 to 4 hours (h) post dose, Cycle 2 Day 1; 3 h post dose; 7 h post dose, Cycle 3 Day 1; pre dose, 3 h post dose)