NCT02324452

Safety, Feasibility and Cost-effectiveness of Genotype-directed Individualized Dosing of Fluoropyrimidines

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,103 (actual)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study it will be determined whether the rate of severe toxicity associated with fluoropyrimidine treatment (capecitabine or 5-fluorouracil) can be significantly diminished by individualized dosing of fluoropyrimidines based on upfront genotypic assessment of dihydropyrimidine dehydrogenase (DPD) deficiency. In addition to the genotyping, the DPD phenotype of all patients will be determined by measuring the baseline dihydrouracil/uracil (DHU/U) ratio, in order to investigate whether phenotype-guided treatment can further improve patient safety. In a subgroup of patients, other phenotyping methods will be tested: measuring the plasma levels of uracil after a uracil test dose and a uracil breath test after a dose of \[2-13C\] -labeled uracil. To validate these tests, these phenotyping results will be compared with the results of a DPD activity assay (which measures DPD enzyme activity in peripheral blood mononuclear cells), which is considered the gold standard in measuring DPD phenotype.

Conditions

• Neoplasms

Interventions

Type	Name	Description
DRUG	Fluoropyrimidine (capecitabine or 5-fluorouracil)	Patient that are a heterozygous carrier of a DPYD variant will receive a reduced dosage of capecitabine or 5-fluorouracil (25-50% reduction, depending on which SNP is identified). The dose will be titrated in subsequent cycles, to achieve maximal safe exposure. Patients that are wild type (not carrying any of the for DPYD variants) will receive a normal (full) dose.

Timeline

• Start date: 2015-03-01
• Primary completion: 2018-01-01
• Completion: 2018-03-01
• First posted: 2014-12-24
• Last updated: 2018-05-11

Locations

17 sites across 1 country: Netherlands