Tailored Treatment in Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Capecitabine, Irinotecan, 5-Fluorouracil+Calciumfolinat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Capecitabine, Irinotecan, 5-Fluorouracil+Calciumfolinat|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point is |  |  | 
| Response according to RECIST criteria. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary end points are |  |  | 
| Progression free survival |  |  | 
| Overall survival |  |  | 
| Toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal cancer, tailored treatment, genetic markers, gene polymorphism, chemotherapy