Clinical trial NCT00138060: Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Metastatic Colorectal Cancer
Keywords: genotypic profile
metastatic colorectal cancer
Lead sponsor: Institut de Recherche Clinique sur les Cancers et le Sang
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2005-08-30
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: tumor response rate
timeFrame: during the treatment
Secondary outcomes:
measure: toxicity
timeFrame: during the treatment
measure: pharmacokinetics
timeFrame: during the first administration
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Department of Oncology, CHU
city: Grenoble
country: France
facility: Department of Oncology, IPC
city: Pierre Benite
country: France
facility: Department of Gastroenterology, CHLS
city: Pierre Benite
country: France
facility: Department of Oncology - CHLS
city: Saint-Priest-en-Jarez
country: France
facility: Department of Oncology, ICL
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: Department of Oncology, CHLS, 69310 Pierre Benite, France
name: Gilles Freyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.