NCT01919229终止2 期
A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 5
- 主要终点
- Cell Cycle Response Rate Per Cell Proliferation Marker Ki67
研究概览
简要总结
This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.
详细描述
This randomized pre-surgical pharmacodynamics study will assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Female patient is ≥ 18 years old at the time of informed consent, with newly diagnosed resectable breast cancer, who received no prior therapy for breast cancer
- •Patient is postmenopausal. Postmenopausal status is defined either by:
- •Prior bilateral oophorectomy
- •Age <60 and amenorrhea for 12 or more months and FSH (Follicle Stimulating Hormone) and estradiol in the postmenopausal range.
- •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 a grade II or grade III invasive breast cancer
- •Patient has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization (respectively FISH/CISH/SISH) test is required) by local laboratory testing
- •Patient has at least one breast lesion with a diameter of ≥1.0 cm by the most accurate imaging modality used.
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
排除标准
- •Patient has received any prior therapy for breast cancer.
- •Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- •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 ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, Long QT Syndrome or conduction abnormality in the previous 12 months.
- •Family history of QTc prolongation or of unexplainable sudden death at <50 years of age.
- •On screening 12 lead ECG, 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 mmHg or <90 mmHg.
- •Patient is currently receiving any of the following medications (see
- •Appendix 1 for details):
- •That are known strong inducers or inhibitors of CYP3A
- •That have a narrow therapeutic window and are predominantly metabolized through CYP3A
- •That have a known risk to prolong the QT interval or induce Torsades de Pointes.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Letrozole
Active Comparator
Letrozole 2.5 mg alone once daily
干预措施: letrozole (Drug)
LEE011 400 mg + letrozole
Experimental
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
干预措施: LEE011 (ribociclib) (Drug)
LEE011 400 mg + letrozole
Experimental
Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.
干预措施: letrozole (Drug)
LEE011 600mg + letrozole
Experimental
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
干预措施: LEE011 (ribociclib) (Drug)
LEE011 600mg + letrozole
Experimental
Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.
干预措施: letrozole (Drug)
结局指标
主要结局
Cell Cycle Response Rate Per Cell Proliferation Marker Ki67
时间窗: Day 1, Day15
Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.
次要结局
- Change From Baseline in Electrocardiogram (ECG) Parameters(Baseline, Day 14)
- Safety and Tolerability of the Combination(Up to 30 days after the last dose)
- Change From Baseline in Expression of Retinoblastoma Protein (pRB)(Baseline, Day 15)
- PK (Pharmacokinetics) Parameters, Including But Not Limited to, Cmax, Tmax, AUClast for LEE011 (and Any Relevant Metabolites) and Letrozole.(Days 1, 8, 14 and 15)
- Change in ECG Morphology(Baseline, Day 14)
- Correlation Between PK Concentrations and ECG Changes(Day 14)
- Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1)(Baseline, Day 15)
研究者
研究点 (5)
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