A Phase 2, Multicenter, Two-Part, Open-Label Study of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor in Japan
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 6
- 主要终点
- Dose-limiting Toxicity (DLT) in Part 1
研究概览
简要总结
This phase 2, multicenter, two-part, open-label, single-arm study will be conducted in Japan and will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of pexidartinib in adult participants with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitation and not amenable to improvement with surgery.
详细描述
This study will consist of 2 parts. In Part 1, pexidartinib 800 mg/day (400 mg twice a day [BID]) will be administered on an empty stomach and tolerability and PK of pexidartinib will be evaluated to determine the initiation of Part 2. In Part 2, pexidartinib 800 mg/day (400 mg BID) will be administered on an empty stomach and efficacy, safety, and PK of pexidartinib will be evaluated.
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
- •Age ≥20 years
- •A diagnosis of TGCT (i) that has been histologically confirmed by a pathologist1 and (ii) associated with severe morbidity or functional limitations and not amenable to improvement with surgery determined consensually by qualified personnel (eg, 2 surgeons or a multi-disciplinary tumor board).
- •Measurable disease as defined by RECIST version 1.1 (except that a minimal size of 2 cm is required), assessed from MRI scan by a central radiologist.
排除标准
- •Known metastatic TGCT.
- •Pre-existing increased serum transaminases; total bilirubin or direct bilirubin (>upper limit of normal); or active liver or biliary tract disease, including increased alkaline phosphatase.
- •Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator's opinion, would likely interfere with a participant's study participation or the interpretation of his or her results.
- •Use of strong cytochrome P450 3A inducers, including St John's wort, proton pump inhibitors and potassium-competitive acid blockers, or other products known to cause hepatotoxicity.
研究组 & 干预措施
Pexidartinib
Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]).
干预措施: Pexidartinib (Drug)
结局指标
主要结局
Dose-limiting Toxicity (DLT) in Part 1
时间窗: Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)
The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed.
Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1
时间窗: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days)
Pharmacokinetic parameters were assessed using non-compartmental methods. Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.
Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of Pexidartinib and ZAAD-1006a (AUClast) in Part 1
时间窗: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days)
Pharmacokinetic parameters were assessed using non-compartmental methods. AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of pexidartinib and ZAAD-1006a in plasma.
Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1
时间窗: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days)
Pharmacokinetic parameters were assessed using non-compartmental methods. AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.
Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1
时间窗: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days)
Pharmacokinetic parameters were assessed using non-compartmental methods. Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2
时间窗: Week 25
ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
次要结局
- ORR Based on Tumor Volume Score (TVS) in Part 2(Week 25)
- Range of Motion (ROM) in Part 2(Week 25)
- Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2(Week 25)
- Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2(Week 25)
- Best Overall Response (BOR) Based on RECIST Version 1.1 in Part 2(Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months)
- BOR Based on TVS in Part 2(Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months)
- Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2(Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months)
- DoR Based on TVS(Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months)
- Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events(Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months)