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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00138060
• Other study ID #: COLOGEN
• Status: Completed
• Phase: Phase 4
• First received: August 26, 2005
• Last updated: July 19, 2010
• Start date: June 2005
• Est. completion date: December 2008

Study information

• Verified date: July 2010
• Source: Institut de Recherche Clinique sur les Cancers et le Sang
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: December 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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

Locations

Country	Name	City	State
France	Department of Oncology, CHU	Grenoble
France	Department of Oncology, IPC	Grenoble
France	Department of Gastroenterology, CHLS	Pierre Benite
France	Department of Oncology - CHLS	Pierre Benite
France	Department of Oncology, ICL	Saint-Priest-en-Jarez
France	Institut Claudius Regaud	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherche Clinique sur les Cancers et le Sang	Pfizer

Country where clinical trial is conducted

France, 

References & Publications (1)

Iyer L, Das S, Janisch L, Wen M, Ramírez 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	tumor response rate		during the treatment	No
Secondary	toxicity		during the treatment	No
Secondary	pharmacokinetics		during the first administration	No