NCT04194957

Improving the Safety of Fluoropyrimidine-based Chemotherapy

Improving the Safety of Fluoropyrimidine-based Chemotherapy by Combined DPYD Genotype-guided and DPD Phenotype-guided Dose Individualization: The ALPE2U Study

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,440 (estimated)
• 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 phenotypic assessment of dihydropyrimidine dehydrogenase (DPD) deficiency.

Detailed description

In this study a phenotypic approach will be studied to determine the additional value of pretreatment uracil level-guided dose individualization in wildtype patients. Patients with a pretreatment serum uracil concentration above 16 ng/ml will be treated with a 50% reduced fluoropyrimidine starting dose. The pretreatment serum uracil levels in DPYD variant carriers will be assessed retrospectively and non-interventional. Additionally, the effect of a higher dose reduction in c.1236G\>A and c.2846A\>T DPYD variants carriers (50% instead of 25%) will be studied.

Conditions

• Neoplasms

Interventions

Type	Name	Description
DRUG	Fluoropyrimidine (capecitabine or 5-fluorouracil)	Patients that are found to be wild type and have a pre-treatment uracil concentration above 16 ng/mL will receive a reduced dosage of capecitabine or 5-fluorouracil (50% reduction). The dose will be titrated after 2 cycles , to achieve maximal safe exposure. Patients that are wildtype with a uracil concentration below 16 ng/mL will receive a normal (full) dose.
DRUG	Fluoropyrimidine (capecitabine or 5-fluorouracil)	Patients that are heterozygous carriers of c.1236G\>A or c.2846A\>T DPYD variant will receive a reduced dosage of capecitabine or 5-FU (50 % reduction). The dose will be titrated after 2 cycles, to achieve maximal safe exposure.
DRUG	Fluoropyrimidine (capecitabine or 5-fluorouracil)	Patients with homozygous or compound heterozygous DPYD variants will be treated with a reduced dose of capecitabine or 5-FU based on the DPD enzyme activity measured in peripheral blood mononuclear cells.

Timeline

• Start date: 2020-01-15
• Primary completion: 2021-01-01
• Completion: 2021-01-01
• First posted: 2019-12-11
• Last updated: 2020-01-22

Locations

1 site across 1 country: Netherlands