Correlation between endogenous DPD substrate concentrations and the pharmacokinetics and toxicity of 5-fluorouracil in patients with colorectal or pancreas cancer

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON21471

Enrollment

Registered

2019-02-19

Start date

2019-03-01

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colorectal or pancreas cancer

Interventions

None listed

Eligibility

Inclusion criteria

Inclusion criteria: 1. Pathologically confirmed malignancy for which treatment with 5-FU is indicated in the FOLFOX, FOLFIRI or FOLFIRINOX regimen. 2. Age = 18 years 3. Able and willing to give written informed consent 4. WHO performance status 0-2 5. Minimal acceptable safety laboratory values defined as a. ANC of = 1.5 x 109 /L b. Platelet count of = 100 x 109 /L c. Hepatic function as defined by serum bilirubin = 1.5 x ULN, ALAT and ASAT = 2.5 x ULN; in case of liver metastases ALAT and ASAT = 5 x ULN. d. Renal function as defined by MDRD >30 mL/min

Exclusion criteria

Exclusion criteria: 1. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient’s safety 2. Women who are pregnant or breast feeding 3. Patients in whom the bolus injection will be skipped due to e.g. toxicity of previous chemo therapy regimen.

Design outcomes

Primary

Measure	Time frame
To determine the correlation between the baseline endogenous DPD substrate plasma ratios of DHU/U and DHT/T with the pharmacokinetics of 5-FU in patients with pancreas or colorectal cancer treated with intravenous 5-FU-based chemotherapy.	—

Secondary

Measure	Time frame
- To determine the potential changes in U, DHU, T and DHT concentrations over time during the prolonged 5-FU infusion - To determine the DHU/U, DHT/T and DHFU/FU ratios over time during 5-FU prolonged infusion - To establish a cut-off concentration in a daily Dutch patient population for all measured analytes, their metabolites and ratios, including 5-FU, DHFU, U, DHU, T and DHT - To determine the effect of DPYD genotype on the U, DHU, T and DHT concentrations and on the pharmacokinetics of 5-FU - To determine the correlation between serious adverse events or 5-FU toxicity to AUC of 5-FU, DHU/U or DHT/T ratio - To determine the effect of other genetic polymorphisms on the pharmacokinetics of 5-FU (if applicable)	—

Measure

Time frame

- To determine the potential changes in U, DHU, T and DHT concentrations over time during the prolonged 5-FU infusion - To determine the DHU/U, DHT/T and DHFU/FU ratios over time during 5-FU prolonged infusion - To establish a cut-off concentration in a daily Dutch patient population for all measured analytes, their metabolites and ratios, including 5-FU, DHFU, U, DHU, T and DHT - To determine the effect of DPYD genotype on the U, DHU, T and DHT concentrations and on the pharmacokinetics of 5-FU - To determine the correlation between serious adverse events or 5-FU toxicity to AUC of 5-FU, DHU/U or DHT/T ratio - To determine the effect of other genetic polymorphisms on the pharmacokinetics of 5-FU (if applicable)

—

Contacts

Public ContactM.A. Hanrath

Catharina ziekenhuis

maarten.hanrath@catharinaziekenhuis.nl0402399111

Outcome results