Identifying Novel Variants in the DPYD Gene in Patients of Non-Western Descent (DPYD-NOW)

Leiden University Medical Center (LUMC)

Status: Unknown

Conditions: Neoplasms

Treatments: Genetic: Sequencing of DPYD gene

Study type: Observational

Funder types: Other

Identifiers

NCT04300361

DPNOW

Details and patient eligibility

About

This is a observational, multicenter study to identify novel variants of the DPYD gene which are possible deleterious in patients of non-Western descent.

Full description

Research has shown that DPYD-guided dose-individualization based on 4 DPYD variants (DPYD*2A, c.1236G>A, c.2846A>T and c.1679T>G) can significantly reduce severe fluoropyrimidine-related toxicity. However, these 4 variants are most likely not predictive for toxicity in patients of non-Western descent. In this study the DPYD gene of patients of non-Western descent will be sequenced to identify novel variants that could be associated with a reduced DPD enzyme activity and an increased risk of developing severe fluoropyrimdine-related toxicity. Additionally, the ability to predict if a DPYD variant is possibly deleterious by a recombinant model systen (DPYD-varifier) will be studied.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pathologically confirmed malignancy for which treatment with a fluoropyrimidine is considered to be in the patient's best interest
• Patients need to be self-declared non-Western
• Age 18 years and older
• Able and willing to give written informed consent
• WHO performance status of 0, 1 or 2
• Life expectancy of at least 12 weeks
• Able and willing to undergo blood sampling for study related analysis
• Adequate baseline patient characteristics (complete blood count, hepatic function which involves serum bilirubin, ASAT, ALAT, and renal function)

Exclusion criteria

• Prior treatment with fluoropyrimidines
• Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient's safety

Trial design

600 participants in 1 patient group

Non-Western patients

Description:

Patients of non-Western descent with an indication for treatment with fluoropyrimidine-based chemotherapy. A patient is classified as non-Western if a one (1) of the parents or more than two (\>2) of the grand parents are of non-Western descent.

Treatment:

Genetic: Sequencing of DPYD gene