Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

This study has been completed.
Sponsor:
Information provided by:
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT00838370
First received: February 5, 2009
Last updated: March 3, 2014
Last verified: March 2014

February 5, 2009
March 3, 2014
May 2007
October 2011   (final data collection date for primary outcome measure)
safety [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00838370 on ClinicalTrials.gov Archive Site
cost-effectiveness [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.

Patients exhibiting a genetically determined disorder (DPYD*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization.

Screening for DPYD*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Neoplasms
Drug: Capecitabine, 5-fluorouracil

Patients to treat with capecitabine/5-FU will be screened prior to start of therapy for DPYD*2A. Patients heterozygous or homozygous mutant for DPYD*2A receive dose reductions of capecitabine/5-FU of at least 50% in the first two courses. In case this dose is tolerated well, doses will be increased.

In addition, the pharmacokinetics of capecitabine/5-FU and their metabolites will be assessed in these patients.

Other Names:
  • Xeloda
  • Capecitabine
  • Fluorouracil
  • 5-Fluorouracil
  • 5-FU
Experimental: DPYD*2A
Patients are screened for a DPD-deficiency. Patients with a DPYD*2A mutation are eligible for intervention with capecitabine/5-FU .
Intervention: Drug: Capecitabine, 5-fluorouracil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
October 2011
October 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histological proof of cancer
  • patient is considered for treatment with capecitabine or 5-FU
  • hetero- or homozygous mutant for DPYD*2A
  • able and willing to give written informed consent
  • able and willing to undergo blood sampling for pharmacokinetic analysis
  • life expectancy 3 months or longer
  • acceptable safety laboratory values (ANC, platelet count, ASAT, ALAT, creatinine,
  • WHO performance status 0-2
  • no radio- or chemotherapy within the last 3 weeks prior to study entry

Exclusion Criteria:

  • patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up
  • women who are pregnant or breast-feeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00838370
NKI-AVL_M07PFU
Yes
Prof. dr. J.H.M. Schellens, The Netherlands Cancer Institute
The Netherlands Cancer Institute
Not Provided
Principal Investigator: Jan HM Schellens, MD, PhD Netherlands Cancer Institute, Amsterdam, the Netherlands
The Netherlands Cancer Institute
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP