An Open-label Study to Assess the Pharmacokinetic Interaction Between Xeloda and Oxaliplatin in Patients With Metastatic Colorectal Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 主要终点
- AUC0-inf for Free Platinum
研究概览
简要总结
This single arm study will investigate possible pharmacokinetic interactions between Xeloda and oxaliplatin, and assess whether the pharmacokinetics of Xeloda and/or oxaliplatin is influenced by the addition of Avastin. All subjects will provide samples for pharmacokinetic analysis during the first 3 cycles of treatment. In cycles 1 and 2 patients will receive a treatment regimen containing Xeloda (1000mg/m2 bid) and oxaliplatin (130mg/m2 iv) and in cycle 3 Avastin (7.5mg/kg iv) will be added to the regimen. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
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
- •adult patients, >=18 years of age;
- •adenocarcinoma of colon or rectum, with metastatic or locally advanced disease.
排除标准
- •previous systemic treatment for advanced or metastatic disease;
- •previous treatment with oxaliplatin or Avastin.
研究组 & 干预措施
1
干预措施: Avastin (Drug)
1
干预措施: Oxaliplatin (Drug)
1
干预措施: capecitabine [Xeloda] (Drug)
结局指标
主要结局
AUC0-inf for Free Platinum
时间窗: Predose , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the 2 hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.
AUC0-infinity represents the area under the concentration-time curve of the analyte (free platinum) in plasma over the time interval from 0 extrapolated to infinity. AUC0-inf for free platinum was calculated for each participant from the concentration-data obtained on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. Free platinum is not bound to plasma proteins and is considered to be the most clinically significant measure of pharmacological and toxicological activity.
Area Under The Plasma Concentration-Time Curve From Zero To Infinity (AUC0-Inf) of 5'-Deoxy-5-fluorouridine 5'-(DFUR)
时间窗: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose.
AUC0-infinity represents the area under the concentration-time curve of the analyte (5'-DFUR) in plasma over the time interval from 0 extrapolated to infinity. The analyte 5'-DFUR, the direct precursor of 5-fluorouracil (5-FU), is considered to be the most important metabolite of capecitabine in plasma. The unit of measure was nanograms per millilitre per hour (ng/mL \* hr).
次要结局
- AUC (0-infinity) of Capecitabine and Its Metabolites (5'-DFCR, 5-FU, and FBAL)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose)
- AUC0-last of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose)
- Maximum Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose)
- Elimination Half-life Period (t1/2 Beta) of Capecitabine and Its Metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)(Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose)
- AUC0-infinity for Total Platinum(Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3)
- AUC0-last of Total And Free Platinum(pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.)
- Cmax of Total And Free Platinum(Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.)
- T1/2 Beta of Total And Free Platinum(Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3)
- Volume of Distribution at Steady State (VSS) of Total And Free Platinum(Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours)
- Clearance of Total And Free Platinum(Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3)
- Number Of Participants With Adverse Events (AEs)(Approximately 3 Years (up to 28 days after the last intake of study medication))
- Marked Laboratory Abnormalities(Up to 28 days after last chemotherapy administration)