A PHASE I/II STUDY OF SUNITINIB IN YOUNG PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 6
- 试验地点
- 9
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite
研究概览
简要总结
Children and young adults with gastrointestinal stromal tumors (GIST) will be treated with sunitinib. The safety (including pharmacokinetics) and tolerability of sunitinib will be studied in these patients. In addition, tumor responses and overall survival will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of GIST.
- •Patients must have demonstrated either disease progression or intolerance to imatinib mesylate, have non-mutant Stem Cell Factor Receptor gene (KIT) GIST, or cannot obtain imatinib in their country
- •Measurable by Response Evaluation Criterion in Solid Tumors (RECIST) or evaluable disease.
排除标准
- •Current treatment with another investigational agent.
- •Prior sunitinib treatment.
- •Prior therapy with known risk for cardiovascular complications.
研究组 & 干预措施
Children with GIST
children ages 6yrs-<18yrs
干预措施: sunitinib malate dose escalation (Drug)
Young adults with GIST
young adults ages 18yrs-<21 yrs
干预措施: sunitinib malate (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite
时间窗: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
AUC(0-8) was defined as area under the plasma concentration time-curve from time zero to 8 hours post dose. SU012662 is the metabolite of Sunitinib.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite
时间窗: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
SU012662 is the metabolite of Sunitinib.
Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite
时间窗: pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1
Estimated steady-state maximum plasma concentration (Cmax,ss) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.
Estimated Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose AUC(0-24) of Sunitinib and Its Metabolite
时间窗: pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1
Estimated area under the plasma concentration versus time curve from time zero to 24 hours post dose (AUC24) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.
Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite
时间窗: pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1
SU012662 is the metabolite of Sunitinib. Oral clearance (CL/F) is a quantitative measure of the rate at which a drug substance is removed from the blood (CL) normalized by the oral bioavailability of the drug (F). Summarized data for all time points was reported.
Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite
时间窗: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
SU012662 is the metabolite of Sunitinib.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0(Baseline up to end of study (up to Cycle 18, each cycle was of 42 days))
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to end of study (up to Cycle 18, each cycle was of 42 days))
- Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to end of study (up to Cycle 18, each cycle was of 42 days))
- Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration(Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)
- Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Efficacy Parameter (e.g., Sum of Largest Diameters for Target Tumors) Was Observed(Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose)
- Number of Participants With Clinically Significant Laboratory Abnormalities(Baseline up to end of study (up to Cycle 18, each cycle was of 42 days))
- Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups(Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days))
- Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration(Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days))
- Number of Participants With Objective Response(Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days))
- Duration of Response(Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days))
- Progression-Free Survival(Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days))
- Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration(Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days))
- Progression Free Survival for PK Subgroups(Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days))
- Overall Survival(Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days))
- Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed(Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose)
- Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups(Baseline until disease progression or discontinuation from the study, or death, whichever occurred first(maximum duration: up to Cycle 18; each cycle was of 42 days))