No registrations found.
ID
Source
Brief title
Health condition
DPD deficiency
Pharmacokinetics
colorectal
DPD deficiëntie
kinetiek
uracil
colorectaal
Sponsors and support
Leids Universitair medische Centum
Leveste Scheper Ziekenhuis
Boermarkeweg 60
7824 AA Emmen
Postadres
Postbus 30.002
7800 RA Emmen
Intervention
Outcome measures
Primary outcome
Compare the AUC of uracil in patients with metastatic colorectal disease and patients with adjuvant treatment.
Secondary outcome
The second objective of the study is to determine if there is a interpatient correlation between uracil levels determined in blood sampled with a newly developed bloodspot mehthod and venapunction.AUC of uracil.
Background summary
Background of the study:
Dihydropyrimidine Dehydrogenase (DPD) is the initial and rate-limiting enzyme in the metabolism of 5-fluorouracil (5-FU).
Patients with a partial or complete DPD deficiency are at risk to develop severe toxicity after 5-FU administration. Uracil is
degraded in dihydrouracil in a similar way as 5-FU. Hypothetically, DPD deficiency may cause higher uracil levels and a reduced
turnover of uracil into dihydrouracil. An oral uracil test dose might be useful to determine the systemic DPD activity by measuring
uracil and its metabolite dihydrouracil in plasma.
Objective of the study:
To compare the pharmacokinetic profile of uracil in cancer patients and healthy volunteers.
Study design:
Case control PK study with 24 patients diagnosed with colorectal cancer.
Study population:
Cancer patients with or without metastasis, age > 18 jaar, DPD activity in PBMC ? 6 nmol/mg/hour treated with 5-FU or
capecitabine.
Intervention:
An oral dose of 500 mg/m2 is adminstered to patients. Bloodsamples are obtained just before and on several timepoints after
dosage.
Primary study parameters/outcome of the study:
AUC of uracil. The second objective of the study is to determine if there is a interpatient correlation between uracil levels
determined in blood sampled with a newly developed bloodspot method and venapunction.
Study objective
Dihydropyrimidine Dehydrogenase (DPD) is the initial and rate-limiting enzyme in the metabolism of 5-fluorouracil (5-FU). Patients with a partial or complete DPD deficiency are at risk to develop severe toxicity after 5-FU administration. Uracil is degraded in dihydrouracil in a similar way as 5-FU. Hypothetically, DPD deficiency may cause higher uracil levels and a reduced turnover of uracil into dihydrouracil. An oral uracil test dose might be useful to determine the systemic DPD activity by measuring uracil and its metabolite dihydrouracil in plasma.
Study design
t = 0, 15, 30, 45, 60, 80, 100, 120, 150, 180 en 240 minutes after intake of uracil.
Intervention
An oral dose of 500 mg/m2 is adminstered to patients. Bloodsamples are obtained just before and on several timepoints after dosage.
Boermarkeweg 60
M. Staveren, van
Emmen 7824 AA
The Netherlands
+31 (0)591 691015
m.vanstaveren@sze.nl
Boermarkeweg 60
M. Staveren, van
Emmen 7824 AA
The Netherlands
+31 (0)591 691015
m.vanstaveren@sze.nl
Inclusion criteria
1. Age > 18 year;
2. Metastatic disease or adjuvant treatment;
3. Signed informed consent;
4. DPD activity in PBMCs ≥ 6 nmol/mg/hr;
5. Live expectation > 3 months.
Exclusion criteria
1. DPD activity in PBMCs < 6 nmol/mg/hr;
2. Pregnancy;
3. Breasfeeding;
4. The use of Cimetidine (regarding drug interactions with 5-fluorouracil and capecitabine);
5. Reduced renal function (creatinine clearance <50 ml/min, calculated with the Cockcroft&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 |
|---|---|
| NTR-new | NL3243 |
| NTR-old | NTR3395 |
| Other | EudraCT : EudraCT2009-017620-11 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |