Phase I Study Of SU011248 In Combination With Oxaliplatin, Leucovorin, And 5-Fluorouracil In Patients With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This study determined the maximum tolerated dose and safety of SU011248 (sunitinib malate, SUTENT) in combination with FOLFOX [Leucovorin + Fluorouracil (5-FU) + Oxaliplatin]. Three different dosing regimens with starting doses of sunitinib at 37.5 mg/day (Schedule 2/2, Schedule 4/2, and Continuous Dosing) were tested in patients with advanced solid tumors, including colorectal cancer.
详细描述
Study Design: Treatment, Single Group Assignment (7 cohorts), Open Label, Non-Randomized, Safety Study.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced solid tumor malignancy (during expansion at the maximum tolerated dose, entry will be limited to patients wtih adenocarcinoma of the colon or rectum)
- •Eastern Cooperative Oncology Group (ECOG) 0 or 1
排除标准
- •Prior treatment with more than 6 cycles of traditional alkylating agent-based chemotherapy regimens
- •Prior treatment with more than 2 cycles of carboplating-based chemotherapy regimens
- •For colorectal cancer patients in the expanded cohorts, prior treatment with more than 2 systemic chemotherapy regimens in the metastatic setting
研究组 & 干预措施
Single arm
SU011248 [sunitinib] in combination with FOLFOX; FOLFOX is a chemotherapy regimen that combines oxaliplatin and leucovorin with bolus and infusion 5-FU. The modified FOLFOX 6 (mFOLFOX6) regimen is one of several different regimens of FOLFOX used in clinic, according to different dosages of the 4 drugs. mFOLFOX6 was administered every 2 weeks on Days 1 and 2 of each cycle.
25, 37.5 and 50 mg/day, oral, administered on an outpatient basis in three different dosing regimens: schedule 2/2 (2 weeks on, 2 weeks off), schedule 4/2 (4 weeks on, 2 weeks off), and continuous daily dosing (every day); FOLFOX will be administered every 2 weeks, using the modified FOLFOX 6 (mFOLFOX6) regimen, consisting of: oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 as a 2-hr IV infusion; 5-FU 400 mg/m2 IV bolus, followed by - 5-FU 2400 mg/m2 as a 46-hr IV infusion
干预措施: sunitinib + FOLFOX (Drug)
结局指标
主要结局
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: up to 20 weeks
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
次要结局
- Tmax of Total Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Objective Response (OR)(From start of treatment until Day 8 of Cycles 4 and 8 (2/2 Schedule), Day 8 of Cycles 3 and 6 (4/2 Schedule), and Day 1 of Cycles 3 and 7 (Continuous Dosing))
- Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Cmax of SU-012662 (Sunitinib's Metabolite)(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Tmax of Free Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Cmax of Total Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Steady State Clearance (CLss) of 5-FU(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- T1/2 of Free Platinum, Total Platinum, and 5-FU(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Time to Cmax (Tmax) of Sunitinib(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Minimum Plasma Concentration (Cmin) of Sunitinib(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Clearance (CL/F) of Sunitinib(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Terminal Phase Half-Life (t1/2) of Sunitinib(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Cmin of SU-012662 (Sunitinib's Metabolite)(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- AUC24 for SU-012662 (Sunitinib's Metabolite)(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose.)
- T1/2 of SU-012662 (Sunitinib's Metabolite)(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Cmax of Free Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- T1/2 for Free Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Maximum Plasma Concentration (Cmax) of Sunitinib(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Tmax of SU-012662 (Sunitinib's Metabolite)(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- CL/F of SU-012662 (Sunitinib's Metabolite)(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Area Under the Curve (AUC) of 5-FU(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Cmin of Free Platinum, Total Platinum, and 5-FU(pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
- Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI(Cycle 3 (Day 1) and Cycle 3 (Day 8))
- Steady State Concentration (Css) of Fluorouracil (5-FU)(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Cmax of 5-FU(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- CL/F of Free Platinum, Total Platinum, and 5-FU(pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose)
- Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)(Cycle 3 (Day 1), Cycle 3 (Day 8))