A Phase I/II Study of Sunitinib Malate (SU011248) In The Treatment of Patients With Malignant Gastrointestinal Stromal Tumor (GIST) Previously Treated by Imatinib Mesylate.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Number of Subjects With Dose Limiting Toxicities (DLT)
研究概览
简要总结
Phase I;To investigate the clinically recommended dose of Sunitinib malate (SU011248) following multiple oral dosing in the first cycle (4 consecutive weeks and 2 weeks rest) by reviewing the safety and tolerability.
Phase II;To determine the objective tumor response and the safety of Sunitinib malate (SU011248) at the clinically recommended dose.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically-confirmed metastatic or unresectable gastrointestinal stromal tumor (GIST).
- •Patients previously treated with imatinib mesylate.
排除标准
- •Patients who have not recovered from the acute toxic effects of previous antineoplastic therapy or treatment with imatinib mesylate.
- •Any tumor therapy for gastrointestinal stromal tumor (GIST) discontinued less than 4 weeks prior to starting study treatment. Imatinib mesylate discontinued less than 2 weeks prior to starting therapy.
研究组 & 干预措施
SU011248
25 , 50 or 75 mg/day of SU011248
干预措施: Sunitinib malate (SU011248) (Drug)
结局指标
主要结局
Number of Subjects With Dose Limiting Toxicities (DLT)
时间窗: Cycle 1 (Baseline to Week 6)
Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1
时间窗: Day 1 of Cycle 1
Maximum Plasma Concentration (Cmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Cmax for total drug (SU-011248+SU-012662) was calculated as the mean of the Cmax of total drug from each individual subject (it is not the simple sum of means of Cmax of SU-011248 and SU-012662).
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28
时间窗: Day 28 of Cycle 1
Maximum Plasma Concentration (Cmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Cmax for total drug (SU-011248+SU-012662) was calculated as the mean of the Cmax of total drug from each individual subject (it is not the simple sum of means of Cmax of SU-011248 and SU-012662).
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1
时间窗: Day 1 of Cycle 1
Area Under the Plasma Concentration Curve (AUC0-24) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The AUC0-24 for total drug (SU-011248+SU-012662) was calculated as the mean of the AUC0-24 of total drug from each individual subject (it is not the simple sum of means of AUC0-24 of SU-011248 and SU-012662).
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28
时间窗: Day 28 of Cycle 1
Area Under the Plasma Concentration Curve (AUC0-24) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The AUC0-24 for total drug (SU-011248+SU-012662) was calculated as the mean of the AUC0-24 of total drug from each individual subject (it is not the simple sum of means of AUC0-24 of SU-011248 and SU-012662).
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1
时间窗: Day 1 of Cycle 1
Time to First Occurrence of Cmax (Tmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Tmax for total drug (SU-011248+SU-012662) was calculated as the median of the Tmax of total drug from each individual subject (it is not the simple sum of median of Tmax of SU-011248 and SU-012662).
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28
时间窗: Day 28 of Cycle 1
Time to First Occurrence of Cmax (Tmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Tmax for total drug (SU-011248+SU-012662) was calculated as the median of the Tmax of total drug from each individual subject (it is not the simple sum of medians of Tmax of SU-011248 and SU-012662).
SU-011248 Clearance on Cycle 1 Day 28
时间窗: Day 28 of Cycle 1
SU-011248 Clearance in the subjects enrolled in Phase 1. Clearance was calculated by dividing a SU-011248 dose(mg) by AUC0-24(ng•h/mL).
Accumulation Ratio (Rac) on Cycle 1 Day 28
时间窗: Day 28 of Cycle 1
Accumulation Ratio (Rac) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) on Cycle 1 Day 28 in the subjects enrolled in Phase 1. Rac was the ratio of Day 28 to Day 1.
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
时间窗: Day 28 of Cycles 1-4
Clinical Benefit Response is defined as sum of subjects confirmed with complete response (CR), partial response (PR), or stable disease (SD)\>= 22 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST).
次要结局
- Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)(Day 1, 14, 28 of Cycles 1-4)
- Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)(Day 1, 14, 28 of Cycles 1-4)
- Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)(Day 1, 14, 28 of Cycles 1-4)
- Trough Plasma Concentration (Ctrough) of SU-011248(Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4)
- Trough Plasma Concentration (Ctrough) of SU-012262(Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4)
- Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662(Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4)
- Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires(Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4)
- Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires(Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4)
- Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group(Day 28 of Cycles 1-4)
- Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group(Day 28 of Cycles 1-4)
- Time To Tumor Progression (TTP)(From the first dose to Progressive Disease)
- Progression-Free Survival (PFS)(From the first dose to Progressive Disease or Death)
- Time To Failure (TTF)(From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or Death due to cancer.)
- Overall Survival Time(From the first dose to death)