Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 20
- 主要终点
- The primary end point is
研究概览
简要总结
To compare the response rate of single agent chemotherapy in advanced colorectal cancer given as standard treatment versus tailored treatment in a randomised phase III trial.
详细描述
The TS and MTHFR polymorphism has been investigated in a new study based on analysis of normal tissue. The results indicated that protein with a 3/3 TS polymorphism or a MTHFR T polymorphism had a significantly higher response rate and a longer time to progression than the other groups when treated with bolus 5-FU.
Capecitabine is metabolised to 5-FU through a number of enzymatic steps. It is the first rationally designed drug that is based upon the high concentration of thymidine phosphorylase (TP) in many human tumors compared to normal tissue. TP is the last step in the conversion of capecitabine to 5-FU and seems to be the limiting factor for the activation. Capecitabine may to some extent mimic continues 5-FU infusion as opposed to bolus 5-FU. A number of small investigations have indicated that patients with 2R/2R TS polymorphism have a higher response rate than heterozygous patients.
The TS and MTHFR polymorphism analysis can easily be performed on sputum, which means an easy collection and sending of the samples.
At present single agent chemotherapy is based on three drugs (5-FU, capecitabine, and Irinotecan) with almost the same overall activity. It seems rational to investigate if improvement can be obtained by tailoring the treatment according to gene polymorphism.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Metastatic colorectal cancer
- •Histopathological verification of the primary tumor
- •Measurable disease according to RESIST criteria
- •Single agent chemotherapy indicated
- •Performance status >=2
- •Age >= 60 years
- •Life expectancy > 3 months
- •Adequate liver and kidney function as evaluated by bilirubin <= 3 times of normal upper limit, ALAT <= 3 times upper normal limit (<= 5 times upper normal limit in case of liver metastases), serum creatinine <= 1.5 times normal upper limit.
- •ANC >=1.5 x 109/l and platelets >= 100 x 109/l
- •Informed consent
排除标准
- •Patients with CNS metastases
- •Other malignant disease within the last 5 years except for non-melanoma skin cancer and carcinoma in situ of cervix uteri
- •Previous chemotherapy for metastatic disease
- •Adjuvant chemotherapy < 6 months before inclusion
- •Patients with previous major toxic or allergic reaction to the protocol drugs
结局指标
主要结局
The primary end point is
Response according to RECIST criteria.
次要结局
- Secondary end points are
- Progression free survival
- Overall survival
- Toxicity