NCT01938638已完成1 期
An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY1143572 Given in a Once-daily or an Intermittent Dosing Schedule in Subjects With Advanced Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 80
- 主要终点
- Number of participants with adverse events as a measure of safety and tolerability
研究概览
简要总结
The purpose of this study Part A is to determine the safety, tolerability and the pharmacokinetics of BAY1143572 in subjects with advanced malignancies, which are either refractory to or ineligible for treatment with standard agents.
The purpose of this study Part B is:
Determine the safety, tolerability, pharmacokinetics (PK) and maximum tolerated dose (MTDG-CSF) of BAY1143572 with concurrent administration of the granulocyte colony-stimulating factors (G-CSF) in an intermittent and continuous dosing schedule in subjects with advanced malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged >/=21 years
- •Dose escalation phase: Subjects with histologically or cytologically confirmed advanced malignancies (solid tumors and malignant lymphomas) who were refractory to or had exhausted all available therapies. Subjects had to have evaluable or measurable disease (as per RECIST 1.1 or Cheson 2007 criteria).
- •Expansion phase only: Subjects with advanced, histologically or cytologically confirmed gastric cancer, triple negative breast cancer (TNBC), or diffuse large B-cell lymphoma (DLBCL), who were refractory to or had exhausted all available therapies. Subjects had to have evaluable or measurable disease (as per RECIST 1.1 or Cheson 2007 criteria).
- •Archival tumor tissue to conduct molecular and / or genetic studies must be collected from all study subjects enrolled in this study.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Life expectancy of at least 12 weeks
- •Adequate bone marrow, liver, and renal functions as assessed by laboratory analysis to be conducted within 7 days prior to the first dose of study drug
- •International normalized ratio (INR) and partial thromboplastin time (PTT) </=1.5 times ULN (upper limit of normal)
排除标准
- •Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study
- •History of cardiac disease including congestive heart failure > New York Heart Association (NYHA) Class II, unstable angina (anginal symptoms at rest) or new-onset angina (within the last 6 months) or myocardial infarction within the past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy except for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (e.g. angina pectoris, myocardial infarction within 6 months prior to study entry, major regional wall motion abnormalities upon baseline echocardiography)
- •Previous pulmonary embolism within 12 months prior to study entry
- •Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg on 2 or more consecutive blood pressure readings, despite optimal medical management
- •Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
- •Known history of human immunodeficiency virus (HIV) infection
- •Chronic or active hepatitis B or C, requiring antiviral therapy
- •Active clinically serious infections of > Grade 2 and/or active infections that require treatment with systemic agent
- •Uncontrolled seizure disorder requiring therapy (such as steroids or anti-epileptics with significant CYP interaction)
- •Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of > Grade 2 within 4 weeks prior to the first dose of study drug
研究组 & 干预措施
BAY1143572 [continuous]
Experimental
BAY1143572 will be administered from cycle 1, day 1 (C1D1) onwards once daily continuously
干预措施: BAY1143572 (Drug)
BAY1143572 [on/off]
Experimental
BAY1143572 will be administered from C1D1 in a 3 days on/4 days off schedule
干预措施: BAY1143572 (Drug)
结局指标
主要结局
Number of participants with adverse events as a measure of safety and tolerability
时间窗: Up to 2 years
Maximum tolerated dose (MTD) of BAY1143572
时间窗: Up to 1 year
In Part A: Maximum tolerated dose (MTD) of BAY1143572 In Part B; Maximum tolerated dose ( MTD) with G-CSF of BAY114357 The MTD is defined as the highest dose that can be given such that not more than 20% of subjects experience a dose limiting toxicity (DLT) during cycle 1.
次要结局
- Maximum total drug concentration (Cmax)(Cycle 1, Day 1 and Day 15 (each cycle is 28 days))
- Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)(Cycle 1, Day 1 and Day 15 (each cycle is 28 days))
- Area under the plasma concentration-time curve from time zero to infinity (AUC)(Cycle 1, Day 1 and Day 15 (each cycle is 28 days))
- Time of maximum observed concentration (tmax)(Cycle 1, Day 1 and Day 15 (each cycle is 28 days))
- Biomarker evaluation by determination of MYC protein expression and PCNA mRNA(Cycle 1, Day 1, Day 8 and Day 15 (each cycle is 28 days))
- Tumor response based on RECIST 1.1 or Cheson 2007 criteria(Up to 100 weeks)
研究者
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