The primary objective of this study is to establish the sensitivity and specificity of an oral uracil loading test as a potential screening tool for DPD deficiency
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the differences in uracil plasma levels and
calculated uracil clearance between cases and controls. Based on these
parameters, the sensitivity and specificity of the oral uracil loading test
will be determined.
Secondary outcome
The secondary objectives of this study are:
• to assess the sensitivity and specificity of the fasting endogenous
uracil/dihydrouracil ratio in blood plasma as a potential screening tool for
DPD deficiency
• to investigate the causes of DPD deficiency and fluoropyrimidine toxicity on
the molecular (genetic) level
Background summary
DPD deficiency is an important risk factor for extreme toxicity during 5-FU or
capecitabine treatment. In DPD deficient patients, the clearance of these drugs
is largely reduced.
Since a cheap, fast, and easy screening method for DPD deficiency is not yet
available, pre-chemotherapy screening is not yet a standard practice. In the
current study, the DPD status is characterized by measuring uracil plasma
levels after oral intake of a 500 mg/m2 uracil test dose. Uracil and 5-FU are
chemically almost alike and both substances are substrates for DPD. Uracil is
an endogenous pyrimidine base and, accordingly, an excellent candidate for DPD
phenotyping.
Study objective
The primary objective of this study is to establish the sensitivity and
specificity of an oral uracil loading test as a potential screening tool for
DPD deficiency
Study design
The study is designed as a multicenter case-control pharmacokinetics study.
A total of 50 DPD deficient patients will be included in the case group and 50
patients with normal DPD activity will be included as controls. The
pharmacokinetics of uracil after oral ingestion of a 500 mg/m2 uracil test dose
will be measured in both groups.
Intensive blood sampling during 4 hours will be performed in 10 patients in
each group. A limited sampling strategy during 2 hours (with a maximum of 2
samples) will be applied in the other 40 patients in each group.
Intervention
Administration of oral uracil followed by blood sampling.
Study burden and risks
Intensive sampling:
No. patients 20
No. extra site visits 1
No. bloodsamples 12*
Total amount of blood 60 ml
Duration of site visit 4-5 uur
Limited sampling:
No. patients 80
No. of extra site visits 1
No. blood samples 3*
Total amount of blood 15 ml
Duration of site visit 2-3 uur
* All patients underwent routine testing for DPD activity in peripheral blood
mononuclear cells. Patients with reduced DPD activity have subsequently been
genotyped for mutations in the DPD gene (DPYD). Both tests can be performed
from a single blood sample.
Hoogeveenseweg 38
7943 KA Meppel
NL
Hoogeveenseweg 38
7943 KA Meppel
NL
Listed location countries
Age
Inclusion criteria
Case group
•Age > 18 years
•More than expected toxicity (grade 3-4, see table 2) after treatment with a 5-FU or capecitabine containing regimen, with clinical suspicions for DPD deficiency. All 5-FU or capecitabine containing chemotherapy schedules are allowed.
•Reduced DPD activity, i.e. < 5 nmol/mg/hour
•Signed informed consent;Control group
•Age > 18 years
•More than expected toxicity (grade 3-4, see table 2) after treatment with a 5-FU or capecitabine containing regimen, with clinical suspicions for DPD deficiency. All 5-FU or capecitabine containing chemotherapy schedules are allowed.
•Normal DPD activity i.e. > 5 nmol/mg/hour
•Signed informed consent
Exclusion criteria
•Pregnancy
•Breast feeding
•Cimetidine use (due to drug-drug interactions with 5-fluorouracil and capecitabine)
•Renal failure (creatinine clearance less than 20 ml/min, calculated with Cockroft&Gault formula).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov, in aanvraag |
| EudraCT | EUCTR2006-002861-37-NL |
| CCMO | NL12893.030.06 |