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

Neoplasms Clinical Trial

— DPYD-NOW  

Official title:

A Prospective, Multicenter, Observational Study to Identify Novel Deleterious Variants in the DPYD Gene in Patients of Non-Western Descent: The DPYD-NOW Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04300361
• Other study ID #: DPNOW
• Status: Not yet recruiting
• Start date: March 1, 2020
• Est. completion date: August 1, 2022

Study information

• Verified date: March 2020
• Source: Leiden University Medical Center
• Contact: Hans Gelderblom, Prof.
• Phone: +31 (0)71 - 526 9111
• Email: a.j.gelderblom[@]lumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 600
• Est. completion date: August 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Genetic:
• Sequencing of DPYD gene
The DPYD gene of non-Western patients will be sequenced to identify DPYD variants that are possibly associated with an increased risk of developing severe fluoropyrimidine-related toxicity.

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
Leiden University Medical Center	Erasmus Medical Center, Haga Hospital, Medical Center Haaglanden, The Netherlands Cancer Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of variants of the DPYD gene that are possibly associated with an increased risk of severe fluoropyrimidine-related toxicity in patients of non-Western descent		Patients will be followed for the first 2 cycles (each cycle is 28 days).
Secondary	DPD enzyme activity of patients carrying a novel DPYD variant compared to wildtype patients measured in peripheral blood mononuclear cells (PBMCs)		Through study completion, an average of 2 years
Secondary	Ability of the DPYD-varifier to predict if a novel DPYD variant is deleterious		Through study completion, an average of 2 years
Secondary	Frequency of DPYD variants per ethnic origin		Through study completion, an average of 2 years
Secondary	Correlation between genetic variants in genes other than DPYD and fluoropyrimidine-related toxicity		Through study completion, an average of 2 years