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

July 19, 2010 updated by: Institut de Recherche Clinique sur les Cancers et le Sang

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

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.

Study Overview

Status

Completed

Conditions

Metastatic Colorectal Cancer

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

France
- - Grenoble, France, 38043
    - Department of Oncology, CHU
  - Grenoble, France, 38100
    - Department of Oncology, IPC
  - Pierre Benite, France, 69310
    - Department of Gastroenterology, CHLS
  - Pierre Benite, France, 69310
    - Department of Oncology - CHLS
  - Saint-Priest-en-Jarez, France, 42271
    - Department of Oncology, ICL
  - Toulouse, France
    - Institut Claudius Regaud

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tumor response rate Time Frame: during the treatment	during the treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
toxicity Time Frame: during the treatment	during the treatment
pharmacokinetics Time Frame: during the first administration	during the first administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut de Recherche Clinique sur les Cancers et le Sang

Collaborators

Pfizer

Investigators

Principal Investigator: Gilles Freyer, MD, Department of Oncology, CHLS, 69310 Pierre Benite, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Iyer L, Das S, Janisch L, Wen M, Ramirez J, Karrison T, Fleming GF, Vokes EE, Schilsky RL, Ratain MJ. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J. 2002;2(1):43-7. doi: 10.1038/sj.tpj.6500072.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

August 26, 2005

First Submitted That Met QC Criteria