Individualization of Dosage of Irinotecan in the FOLFIRI According to the Genetic Polymorphism of UGT1A1 in the First Line Treatment of Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This prospective, non randomized multicenter phase II study, will determine the feasibility of individualized dose of irinotecan with the UGT1A1 polymorphism, in patients with metastatic colorectal cancer treated with FOLFIRI.

Official Title
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Phase II Study: Individualization of Dosage of Irinotecan in the FOLFIRI According to the Genetic Polymorphism of UGT1A1 in the First Line Treatment of Metastatic Colorectal Cancer

Conditions
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First Line Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Colorectal cancer histologically or cytologically proven Indication of treatment according to the FOLFIRI + / - bevacizumab or cetuximab or panitumumab Age> 18 years Presence of at least one measurable target by RECIST Life expectancy> 3 months Satisfactory biological functions (renal, hepatic and hematologic) Affiliation to a social security scheme (or be the beneficiary of such a plan) under the terms of the Act of August 9, 2004 Patient has signed, after informing the informed consent form Exclusion Criteria: Patients of childbearing age and not using effective contraception during treatment and for at least three months after the end of treatment with irinotecan and at least six months after the end of treatment with bevacizumab, cetuximab or panitumumab and patient pregnant or nursing Patient with another pathology deemed incompatible with the entry in the protocol Prior treatment in metastatic Patients taking antiepileptic Allergic reaction or intolerance to irinotecan Heart failure , kidney , bone marrow , liver or respiratory Higher bilirubin 1.5 times the upper limit of normal Significant psychiatric or neurological abnormality Infectious syndrome requiring treatment with antibiotics or antiviral long-term Patients with chronic inflammatory bowel disease and / or bowel obstruction Contraindication Association St. John's wort and yellow fever vaccine Against Heart indication 5-FU Concurrent treatment with a drug test , participation in a clinical trial within <30 days Patient refused to sign the consent

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: irinotecan dose based on genetic polymorphism of UGT1A1<br> | Drug: Irinotecan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| severe toxicity (according to NCI-CTC cotation) and response with adapted dose of irinotecan |  | during the treatment (an expected average of 7 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study of the blood concentration (pharmacokinetic) of irinotecan, the SN38 and SN38-G, and bevacizumab |  | during the first 24 hours of the first cure | 
| evaluation of treatment efficacy (progression-free survival, duration of response) |  | to progression (1 year) |