An Open-label Phase I Study of Oral ASP5878 at Single and Multiple Doses in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 35
- 主要终点
- Dose-escalation part and Expansion part:Safety assessed by Body weight
研究概览
简要总结
The objectives of this study are to determine the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of oral ASP5878 in participants with solid tumors.
详细描述
This study consists of two parts. In the dose-escalation part, ASP5878 (orally available novel small-molecule FGFR 1,2,3 and 4 inhibitor, multiple dosing once-a-day (q.d.), multiple dosing twice-a-day (b.i.d.) or 5-day on/2-day off dosing twice-a-day (5on-2off)) is administered to participants with solid tumors in an increasing dose manner, and the tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of ASP5878 are evaluated in these participants. Cycle 0 consists of 3 days and Cycle 1 and subsequent cycles consist of 28 days each in the dose-escalation part. In the expansion part, 16mg twice-a-day 5-day on/2-day off dose of ASP5878 (5on-2off) is administered to participants with solid tumors and safety, PK, PD and efficacy of ASP5878 are evaluated. The expansion part starts from Cycle 1 and each cycle consists of 28 days.
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
- 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
- •Histologically or cytologically confirmed solid tumor.
- •Participant must meet at least one of the following criteria in the judgment of the investigator or sub-investigator:
- •Disease progression despite standard therapies
- •Progressive disease without any standard therapies established
- •Standard therapies are considered intolerable
- •Eastern Cooperative Oncology Group performance status 0 or
- •Predicted life expectancy ≥ 12 weeks in the judgment of the investigator or sub-investigator.
排除标准
- •Participant with ≥ Grade 2 (CTCAE v 4.0-JCOG) persistent symptoms and objective findings due to the toxicity attributable to prior treatment with antitumor effect (except alopecia).
- •Participant who received a prior treatment intended for antitumor effect (medication, surgery, radiotherapy, etc.) within 4 weeks prior to the planned first day of study drug dosing (or participant who received mitomycin C or Nitrosourea within 6 weeks prior to the planned first day of study drug dosing).
- •A major surgical procedure within 4 weeks prior to the planned first day of study drug dosing or a surgical procedure is planned during the course of the study.
- •Participant who were treated with other investigational drug or medical device within 4 weeks prior to the planned first day of study drug dosing.
- •Participant who has a history of organ transplantation.
- •Participant with a brain metastasis with symptoms or requiring treatment.
研究组 & 干预措施
Expansion part Urothelial Carcinoma
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 1.0 mg QD
Oral
干预措施: ASP5878 (Drug)
Expansion part Squamous Cell Lung Carcinoma
Oral
干预措施: ASP5878 (Drug)
Expansion part Hepatocellular Carcinoma
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 16.0 mg BID
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 4.0 mg BID
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 2.0 mg QD
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 20.0 mg BID
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 10.0 mg BID
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 6.0 mg BID
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 2.0 mg BID
Oral
干预措施: ASP5878 (Drug)
Dose escalation part 0.5 mg QD
Oral
干预措施: ASP5878 (Drug)
结局指标
主要结局
Dose-escalation part and Expansion part:Safety assessed by Body weight
时间窗: Up to 18 months
Until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part: Computed tomography (CT) Imaging assessment
时间窗: Up to 18 months
Until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part:Safety assessed by Vital signs
时间窗: Up to 18 months
Blood pressure, pulse rate and body temperature, Until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part: Ophthalmology
时间窗: Up to 18 months
Eyesight, funduscopy, slit lamp microscopy, and Optical Coherence Tomography, until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part:Safety assessed by Laboratory tests
时间窗: Up to 18 months
Hematology, blood biochemistry, blood coagulation tests and urinalysis, until one of the discontinuation criteria is met.
Expansion part only: Echocardiogram
时间窗: Up to 18 months
Until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part:Safety assessed by 12-lead ECGs
时间窗: Up to 18 months
ECG: Electrocardiogram, until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part: Safety assessed by Adverse Events (AEs)
时间窗: Up to 18 months
Until one of the discontinuation criteria is met.
Dose-escalation part and Expansion part: Bone density measurement
时间窗: Up to 18 months
Until one of the discontinuation criteria is met.
次要结局
- Expansion part: Overall response(Up to 18 months)
- Dose-escalation part:PK parameter of ASP5878 in plasma: tmax(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part:PK parameter of ASP5878 in plasma: AUClast(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PD parameter: Serum inorganic phosphorus concentrations(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: AUCinf(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: Vz/F(Day 1 and 5 at Cycle 1)
- Expansion part: PD parameter: Serum FGF23 concentrations(Up to 18 months)
- Expansion part: PD parameter: Serum iPTH concentrations(Up to 18 months)
- Expansion part: PD parameter: Serum calcitriol concentrations(Up to 18 months)
- Dose-escalation part: Pharmacokinetics (PK) parameter of ASP5878 in plasma: Cmax(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PK parameter of ASP5878 in plasma: AUCinf(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PK parameter of ASP5878 in plasma: t1/2(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PK parameter of ASP5878 in urine: Ae(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PD parameter: Serum calcium concentrations(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PD parameter: Serum calcitriol concentrations(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Expansion part: Progression free survival (PFS)(Up to 18 months)
- Dose-escalation part: PK parameter of ASP5878 in plasma: CL/F(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PK parameter of ASP5878 in plasma: Vz/F(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: Cmax(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: AUClast(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: t1/2(Day 1 and 5 at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: CL/F(Day 1 and 5 at Cycle 1)
- Expansion part: PD parameter: Serum 7α-hydroxy-4-cholesten-3-one(Up to 18 months)
- Expansion part: Maximum Shrinkage in Target Lesion(Up to 18 months)
- Expansion part: Overall survival (OS)(Up to 18 months)
- Dose-escalation part: PK parameter of ASP5878 in urine: CLR(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Expansion part: PD parameter: Serum FGF19 concentrations(Up to 18 months)
- Expansion part: Time to progression (TTP)(Up to 18 months)
- Dose-escalation part: Pharmacodynamic (PD) parameter: Serum FGF23 concentrations(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Dose-escalation part: PD parameter: Serum iPTH concentrations(Day 1 at Cycle 0 and Day 5 (5on-2off) or 27 (q.d./b.i.d.) at Cycle 1)
- Expansion part: PK parameter of ASP5878 in plasma: tmax(Day 1 and 5 at Cycle 1)
- Expansion part: PD parameter: Serum inorganic phosphorus concentrations(Up to 18 months)
- Expansion part: Time to treatment failure (TTF)(Up to 18 months)