A Randomized, Open-Label, Phase 2 Study of Abemaciclib Plus Tamoxifen or Abemaciclib Alone, in Women With Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 234
- 试验地点
- 59
- 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 the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic breast cancer.
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
- None
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 HR+, HER2- breast cancer.
- •Relapsed or progressed following endocrine therapy.
- •Have received prior treatment with at least 2 chemotherapy regimens, of which at least 1 but no more than 2 have been administered in the metastatic setting.
- •Have the presence of measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- •Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- •Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy.
- •Have adequate organ function.
- •Have negative serum pregnancy test within 7 days prior to the first dose of study treatment and agree to use highly effective precautions to prevent pregnancy during the study and for 3 weeks following last dose of study treatment.
- •Are able to swallow oral medication.
排除标准
- •Have clinical evidence or history of central nervous system metastasis.
- •Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
- •Have active bacterial or fungal infection (that is, requiring intravenous antibiotics at the time of initiating study treatment) and/or detectable viral infection.
- •Have received treatment with a prior cyclin-dependent kinase (CDK4) and CDK 6 inhibitor.
- •Have a preexisting chronic condition resulting in persistent diarrhea.
- •Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix or breast), unless in complete remission with no therapy for a minimum of 3 years.
研究组 & 干预措施
Abemaciclib + Tamoxifen
Abemaciclib given orally every 12 hours (Q12H) in combination with tamoxifen given orally every day. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Abemaciclib + Tamoxifen
Abemaciclib given orally every 12 hours (Q12H) in combination with tamoxifen given orally every day. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Tamoxifen (Drug)
Abemaciclib
Abemaciclib given orally Q12H. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Abemaciclib + Prophylactic Loperamide
Abemaciclib given orally Q12H in combination with prophylactic loperamide given orally. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Abemaciclib + Prophylactic Loperamide
Abemaciclib given orally Q12H in combination with prophylactic loperamide given orally. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Prophylactic Loperamide (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months)
Progression-free survival time was measured from the date of randomization to the date of investigator-determined objective progression as defined by RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is defined as 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. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available.
次要结局
- Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months))
- Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and Its Metabolites(Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose)
- PK: Multiple Dose Concentration of Tamoxifen and Endoxifen(Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose)
- PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen(Cycle 1 Day 1 post dose)
- Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)(Baseline to Objective Disease Progression (Up to 21 Months))
- Overall Survival (OS)(Baseline to Death from Any Cause (Approximately 36 Months))
- Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and Its Metabolites(Cycle (C) 1 Day (D) 1 post dose)
- Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)(Baseline, 21 Months)
- Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)(Baseline, 21 Months)