NCT02154776已完成1 期
A Phase 1 Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole for the Treatment of HR+, HER2-negative Post-menopausal Women With Locally Advanced or Metastatic Breast Cancer.
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a multi-center, open-label, non-randomized, phase I study
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease.
- •Patient is postmenopausal.
- •Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase.
- •Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
- •Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
- •Patient must have either:
- •Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion
排除标准
- •Patient who received any CDK4/6 or PI3K inhibitor.
- •Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
- •History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
- •History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- •Documented cardiomyopathy
- •Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- •History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
- •On screening, any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec.
- •Systolic blood pressure >160 or <90 mmHg
- •Patient is currently receiving any of the following medications:
- •That are known strong inducers or inhibitors of CYP3A
- •That have a known risk to prolong the QT interval or induce Torsades de Pointes.
- •That have a narrow therapeutic window and are predominantly metabolized through CYP3A
- •Certain scores on an anxiety and depression mood questionnaires
研究组 & 干预措施
LEE011 + buparlisib + letrozole
Experimental
open label, dose escalation evaluating max tolerated dose of the triple combination
干预措施: LEE011 (Drug)
LEE011 + buparlisib + letrozole
Experimental
open label, dose escalation evaluating max tolerated dose of the triple combination
干预措施: Buparlisib (Drug)
LEE011 + buparlisib + letrozole
Experimental
open label, dose escalation evaluating max tolerated dose of the triple combination
干预措施: Letrozole (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: 28 days
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle
Safety and tolerability of the combination of LEE011, buparlisib, and letrozole
时间窗: approximately 25 months
Dose Expansion Phase: Incidence of AEs, SAEs (overal and severity), laboratory abnormalities, ECG, vital, dose interteruptions, dose reductions, and dose intensity as a measure of safety and tolerability.
次要结局
- Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole(approximately 25 months)
- Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles(approximately 25 months)
- Disease control rate(approximately 25 months)
- PFS (progression free survival)(approximately 25 months)
研究者
研究点 (6)
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