Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants

Study Overview
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Brief Summary
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This study intends to optimize a fluorouracil/irinotecan chemotherapy regimen by the identification of individual thymidylate synthase (TS) and UDP-glucuronosyltransferase 1 (UGT1A1) polymorphisms before the first administration. The results of this identification determine the chemotherapy type: high-dose irinotecan or not.

Official Title
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Protocole Evaluant Chez Des Patients Porteurs de Cancers Colorectaux Metastatiques l'Interet Des Determinants Genotypiques Pour l'Optimisation de l'Efficacite et de la Tolerance de la Chimiotherapie Par Irinotecan et 5-fluorouracile

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: irinotecan
* Drug: 5 fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has provided written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time without prejudice Ages between 18 and 85 years Histologically confirmed colorectal cancer No treatment for metastatic disease No irinotecan previously administered World Health Organization (WHO) performance status < 3 Laboratory values : neutrophils > 1.5 x 10^9/L; platelet count > 100 x 10^9/L; serum creatinine < 130µmol/L; serum bilirubin < 2 x upper limit of normal (ULN); ASAT and ALAT < 2.5 x ULN; alkaline phosphatase < 5 x ULN. At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Exclusion Criteria: History of another malignancy except cured basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix, breast or bladder. Other concomitant anticancer therapy. Pregnant or lactating women. Women of childbearing potential unless using a reliable and appropriate contraceptive method. Symptomatic cerebral or leptospiral metastasis. Intestinal obstruction. Uncontrolled seizures (diabetes, severe infection). Clinically significant cardiac disease. Central nervous system disorders or severe psychiatric disability. Participation in any investigational study within 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: irinotecan|180 mg/m² or 260 mg/m² in 90 minutes every 15 days|
|Drug: 5 fluorouracil|400 mg/m² in bolus in day 1 and 2400 mg/m² in 46 hours perfusion|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor response rate |  | during the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| toxicity |  | during the treatment | 
| pharmacokinetics |  | during the first administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genotypic profile, metastatic colorectal cancer