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

NCT04300361 | Unknown DMC FDA Drug

• 1 other identifier: DPNOW
• Study Type: observational
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Neoplasms

Keywords

Fluoropyrimidines; DPYD; Genotyping; Capecitabine; 5-Fluorouracil; 5-FU; Non-Western

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• Ability of the DPYD-varifier to predict if a novel DPYD variant is deleterious

  Through study completion, an average of 2 years

• Frequency of DPYD variants per ethnic origin

  Through study completion, an average of 2 years

• Correlation between genetic variants in genes other than DPYD and fluoropyrimidine-related toxicity

  Through study completion, an average of 2 years

Study Arms (1)

Non-Western patients

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.

Genetic: Sequencing of DPYD gene

Interventions

Sequencing of DPYD gene GENETIC

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.

Non-Western patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Non-western patients with an indication for treatment with fluoropyrimidine-based chemotherapy. A patient is classified as non-Western if 1 of the parents or \> 2 of the grandparents are of non-Western descent.

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• The Netherlands Cancer Institute: collaborator
• Erasmus Medical Center: collaborator
• Haga Hospital: collaborator
• Medical Center Haaglanden: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

1. blood sample (whole blood) of 4 ml (EDTA-tube) for sequencing of the DPYD gene 2. blood samples (whole blood) of 6 ml (EDTA-tubes) each for determination of the DPD enzyme activity

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Hans Gelderblom, Prof.

CONTACT

+31 (0)71 - 526 9111; a.j.gelderblom@lumc.nl

Jesse Swen, PhD

CONTACT

+31 (0)71 - 5262790; j.j.swen@lumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: March 9, 2020
• Study Start: March 1, 2020
• Primary Completion: March 1, 2022
• Study Completion: August 1, 2022
• Last Updated: March 9, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share