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.

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Capecitabine, 5-fluorouracil

Drug

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

Primary outcomes

safety

Time frame: during fluoropyrimidine treatment of the patient

Secondary outcomes

cost-effectiveness

Time frame: during fluoropyrimidine treatment of the patient

Sponsors and collaborators

Lead sponsor

The Netherlands Cancer Institute

Other

Registry information

Important dates

Study start: 2007
Primary completion: 2011
Study completion: 2011
First posted: Feb 6, 2009
Registry last updated: Mar 4, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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