A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination With Intramuscular (IM) Fulvestrant to Patients With Estrogen Receptor Positive (ER+) Advanced, Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 99
- 试验地点
- 5
- 主要终点
- Adverse Events
研究概览
简要总结
The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant
详细描述
A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination with Intramuscular (IM) Fulvestrant to Patients with Estrogen Receptor Positive (ER+) Advanced, Metastatic Breast Cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated written informed consent prior to any study specific procedures, sampling analysis
- •Aged at least 18
- •At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment
- •Histological or cytological confirmation of an ER+ advanced metastatic breast cancer tumour that is eligible for treatment with fulvestrant
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients must have evidence of non-child-bearing potential.
排除标准
- •Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents, and any investigational agents within 14 days of starting study treatment (not including palliative radiotherapy at focal sites)
- •Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study.
- •Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions.
- •Patients with diabetes type 1 or uncontrolled type II (HbA1c > 8% assessed locally)
研究组 & 干预措施
AZD2014 with Fulvestrant
AZD2014 with Fulvestrant
干预措施: AZD2014 (Drug)
AZD2014 with Fulvestrant
AZD2014 with Fulvestrant
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Adverse Events
时间窗: Up to 12 Months
Adverse Events Leading to Dose Reduction of AZD2014
时间窗: Up to 28 Days
Clinically Important Changes in Clinical Chemistry Parameters
时间窗: Up to 12 Months
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
时间窗: 5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
时间窗: 5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
时间窗: 5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
时间窗: 5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
时间窗: 5 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
时间窗: 15 Days
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
时间窗: 15 Days
Clinically Important Changes in Haematology Parameters
时间窗: Up to 12 Months
Left Ventricular Ejection Fraction
时间窗: 24 hours
QTcF Over 24 Hours
时间窗: 24 hours
Post-Baseline Glucose Elevation
时间窗: 28 Days
Sitting Diastolic Blood Pressure
时间窗: 28 Days
Sitting Systolic Blood Pressure
时间窗: 28 Days
Respiratory Rate
时间窗: 28 Days
Heart Rate
时间窗: 28 Days
Body Temperature
时间窗: 28 Days
Oxygen Saturation
时间窗: 28 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant
时间窗: 15 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
时间窗: 22 Days
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
时间窗: 22 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant
时间窗: 15 Days
次要结局
- AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.(1 Day)
- Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.(1 Day)
- Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.(1 Day)
- Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.(1 Day)
- Objective Response Rate(Up to 12 months)
- Best Objective Response (BOR)(Up to 12 months)
- Duration of Response (DoR)(Up to 12 months)
- Clinical Benefit Rate (CBR) at 24 Weeks(Up to 12 months)
- Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.(Up to 12 months)
- Progression Free Survival(Up to 12 months)
- Progression Free Survival at 26 Weeks(Up to 12 months)