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

NCT02324452 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 1103

Last updated 2018-05-11

No results posted yet for this study

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

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.

Sponsors & Collaborators

  • The Netherlands Cancer Institute

    lead OTHER

Principal Investigators

  • JHM Schellens, MD, PhD · The Netherlands Cancer Institute

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-03-31
Primary Completion
2018-01-31
Completion
2018-03-31

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02324452 on ClinicalTrials.gov