A Phase 1 Study of TAS-116 (Pimitespib) in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumor
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 78
- 试验地点
- 14
- 主要终点
- Maximum tolerable dose (MTD) of pimitespib in combination with imatinib
研究概览
简要总结
This study consists of Dose escalation part and Expansion part. In Dose Escalation Part, the maximum tolerated dose of combination of pimitespib and imatinib in patients with gastrointestinal stromal tumors (GIST) who are judged to be refractory to imatinib, estimate the recommended dose, evaluate safety and pharmacokinetics, and observe the antitumor effect. Expansion part consists of 3 arms. In Arm A, the efficacy and safety will be evaluated, which of the combination of pimitespib and imatinib in patients with GIST who have failed imatinib at doses below the MTD determined in Dose Escalation Part. In Arm B, the efficacy and safety of pimitespib monotherapy will be evaluated and the therapeutic effect of imatinib administration after pimitespib will be evaluated in an exploratory manner. In Arm C, the efficacy and safety of sunitinib monotherapy will be evaluated as reference data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provided written informed consent
- •Histologically confirmed GIST
- •Has radiographic progression based on RECIST 1.1 during or within 6 months of the last imatinib administration at enrollment. If surgery/radiotherapy has been performed, radiographic progression based on RECIST 1.1 with imatinib must have been observed after the last surgery /radiotherapy
- •Has at least one measurable lesion based on the RECIST version 1.1, except lymph nodes (not dependent on size), which should be chosen as nontarget lesions;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
排除标准
- •Corrected visual acuity < 0.5 (using the International Visual Acuity Measurement Standard) for both eyes
- •Received treatment with any other line of therapy besides imatinib for advanced GIST
- •History of total gastrectomy and/or whole resection of the small intestine
- •A serious illness or medical condition
- •Previous or concurrent cancer that is distinct in primary disease or histology from cancer that is being evaluated in this study. However, any previous cancer curatively treated > 5 years before the enrollment can be eligible
- •Pregnancy or lactation (including lactation interruption)
研究组 & 干预措施
Dose Escalation Part
Pimitespib in combination with imatinib
干预措施: Pimitespib (Drug)
Dose Escalation Part
Pimitespib in combination with imatinib
干预措施: Imatinib (Drug)
Expansion Part-C
Sunitinib
干预措施: Sunitinib (Drug)
Expansion Part-A
Pimitespib in combination with imatinib
干预措施: Pimitespib (Drug)
Expansion Part-A
Pimitespib in combination with imatinib
干预措施: Imatinib (Drug)
Expansion Part-B
Pimitespib followed by imatinib
干预措施: Pimitespib (Drug)
Expansion Part-B
Pimitespib followed by imatinib
干预措施: Imatinib (Drug)
结局指标
主要结局
Maximum tolerable dose (MTD) of pimitespib in combination with imatinib
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Progression-free survival (PFS)
时间窗: approximately 2 years
次要结局
- Time to reach maximum plasma concentration (Tmax)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Under the plasma concentration-time curve up to the last observable concentration (AUC0-last)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- λz(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Half-life (T1/2)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Oral clearance (CL/F)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Adverse drug reaction (ADR)(approximately 2 years)
- Maximum plasma concentration (Cmax)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Overall response rate (ORR)(approximately 2 years)
- Duration of response (DoR)(approximately 2 years)
- Adverse event (AE)(approximately 2 years)
- Overall survival (OS)(approximately 2 years)
- Disease control rate (DCR)(approximately 2 years)
- Apparent volume of distribution (Vz/F)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Mean residence time (MRT)(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Accumulation ratio(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))
- Metabolite ratio(Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days))