An Open Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BAY 1163877 in Japanese Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 9
- 主要终点
- Cmax divided by dose (mg) per kg body weight (Cmax,norm) of BAY1163877
研究概览
简要总结
Primary objectives of this study are to assess the safety and tolerability of BAY 1163877 in Japanese subjects with refractory, locally advanced or metastatic solid tumors and to characterize the PK of BAY 1163877
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Japanese males or female aged ≥ 20 years
- •Histologically or cytologically confirmed refractory, locally advanced or metastatic solid tumors who are not candidates for standard therapy at discretion of investigator
- •High FGFR expression levels based on archival or fresh tumor biopsy specimen analysis. Bladder cancer subjects with low overall FGFR expression levels can be included if activating FGFR3 mutations are confirmed.
- •Subjects must have at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
- •Life expectancy of at least 3 months
- •Recovery to National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v4.03) Grade < 2 level or recovery to baseline preceding the prior treatment from any previous drug / procedure-related toxicity (subjects with persistent alopecia, anemia, and/or hypothyroidism can be included)
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
- •Adequate bone marrow, liver and renal function
- •Prothrombin time-International normalized ratio (PT-INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN. Subjects being treated with anticoagulant, e.g. warfarin or heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists
排除标准
- •History or current condition of an uncontrolled cardiovascular disease including congestive heart failure New York Heart Association (NYHA) > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
- •Left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiography performed
- •Subjects with history and/or current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis). Calcium (Ca) x (time) phosphate (PO4) should be < 70 mg²/dL².
- •Current evidence of corneal disorder / keratopathy including but not limited to bullous / band keratopathy, corneal abrasion, inflammation / ulceration, keratoconjunctivitis etc. (to be confirmed by ophthalmologic examination). Pre-existing cataract is not an exclusion criterion.
- •Moderate or severe hepatic impairment (subjects with Child-Pugh score B or C cannot be included.)
- •Known human immunodeficiency virus (HIV) infection
- •Subjects with an active hepatitis B and/or C infection requiring treatment
- •Anticancer chemotherapy or immunotherapy during the study or within 5-half-lives of anticancer chemotherapy or immunotherapy before start of study treatment.
- •Systolic blood pressure ≤ 110 and pulse rate ≥ 100/min, or diastolic blood pressure ≤ 70 mmHg and pulse rate ≥ 100/min
- •Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg at screening
研究组 & 干预措施
BAY1163877
Cohort 1: Safety, tolerability and PK of 600 mg dose given twice daily. Escalation to cohort 2 in case no safety relevant adverse event has been observed within 21 days after start of study treatment Cohort 2: Safety, tolerability and PK of 800 mg dose given twice daily
干预措施: BAY1163877 (Drug)
结局指标
主要结局
Cmax divided by dose (mg) per kg body weight (Cmax,norm) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Number of an Treatment Emergent Adverse Event
时间窗: Up to 35 days after the last study drug administration
Intensity of an Treatment Emergent Adverse Event graded using the NCI-CTCAE version 4.03
时间窗: Up tp 35 days after the last study drug administration
Maximum observed plasma concentration after single dose administration (Cmax) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Cmax divided by dose (mg) (Cmax/D) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Area under the plasma concentration vs time curve from zero to 12 hours p.a. after first-dose administration (AUC(0-12)) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
AUC(0-12) divided by dose (mg) per kg body weight (AUC(0-12) norm) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
AUC(0-12) divided by dose (mg) (AUC(0-12)/D) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
AUC from time zero to the last data point > LLOQ (lower limit of quantification) of BAY1163877 (AUC(0-tlast))
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC(0-tlast) divided by dose (mg) per kg body weight (AUC(0-tlast) norm) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC(0-tlast) divided by dose (mg) (AUC(0-tlast)/D) of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUCnorm of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC/D of BAY1163877
时间窗: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Maximum Observed Drug Concentration in Plasma after multiple administrations (Cmax, md) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax after multiple administrations divided by dose (mg) per kg body weight (Cmax,norm, md) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12) divided by dose (mg) after multiple administrations (AUC(0-12)/Dmd) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast)after multiple administrations (AUC(0-tlast)md) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-tlast) norm,md) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax after multiple administrations divided by dose (mg) (Cmax/Dmd) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12) after multiple administrations (AUC(0-12)md) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-12)norm,md) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast) after multiple administrations divided by dose (mg) (AUC(0-tlast)/Dmd) of BAY1163877
时间窗: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
次要结局
- Tumor response evaluation based on RECIST 1.1(Screening, end of every second cycle (i.e., Cycle 2, 4, 6, 8,…))
- FGF23 levels(Cycle 1 (Days 1 and 15))
- Phosphate levels(Cycle 1 (Days 1, 8, 15), Cycle 2 to 12 (Days 1, 8, 15), Cycle ≥13 (Days 1, 11), end of treatment)
- FGFR1/2/3 mRNA expression in tumor tissue to evaluate of biomarker status(At Screening visit)