Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines.

NCT ID: NCT05266300

Last Updated: 2022-11-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 722 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2022-10-01

Brief Summary

The purpose of this study is to examine the benefits of a clinical implementation of a DPYD-genotype test to patients starting treatment with fluoropyrimidines (Fluorouracil (5-FU), capecitabine, tegafur).

Detailed Description

Patients with specific genetic mutations in the DPYD-gene have lower activity of the dihydropyrimidine dehydrogenase (DPD) enzyme, which is the rate-limiting enzyme in the metabolism of fluoropyrimidines. Fluoropyrimidines are commonly used as chemotherapeutic drugs and include 5-Fluorouracil, capecitabine, and tegafur. Patients with decreased DPD activity are at higher risk of serious adverse events when treated with standard doses of fluoropyrimidines

This study will examine the clinical implementation of the pre-emptive DPYD-genotype test. The test will analyze four of the most common genetic mutations(SNPs) in the DPYD-gene that leads to significant decreased DPD-activity

In patients with DPYD-variant mutations, the recommended starting dose is 50%. This dose reduction will possibly reduce the rate of serious adverse events. Patients who are homozygous or compound heterozygous for a DPYD-mutation will not be treated with fluoropyrimidines due to the high risk of fatal adverse effects.

Aim To reduce the overall incidence of severe adverse reactions(grade >= 3) to chemotherapy regimens containing 5-FU, capecitabine, or S1 in an unselected population of colorectal, non-colorectal GI cancer, or breast cancer patients through pre-emptive DPYD-genotyping.

Design The investigators will conduct an open clinical trial using historical controls. The investigators will implement pre-emptive genotype testing of about 1000 consecutive patients subject to 5-FU, capecitabine, or S1 treatment for colorectal, non-colorectal GI, or breast cancer. The investigators will use a historical control group of about 500 consecutive similar patients.

Genotype and Phenotype Patients included in the study who are genotyped for DPYD will have blood collected for a post hoc phenotype test. The blood samples will be used to measure levels of uracil.

Some patients in the historic cohort have donated blood to an independent biobank at the time of their cancer treatment. These samples will be used for post hoc DPYD-genotype analysis after the necessary ethical approvals.

Cost-effectiveness An economic analysis will be undertaken to examine if implementing the DPYD-genotype is cost-effective.

Conditions

Adverse Drug Event; Colon Cancer; Breast Cancer; Pancreas Cancer; Rectal Cancer; Gastric Cancer; Oesophageal Cancer; Bile Duct Cancer

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Retrospective

Historic group. Patients treated in the historic control group did not receive DPYD-genotype before treatment with fluorouracil, capecitabine, tegafur. They received standard start doses of 5-FU, capecitabine, tegafur.

No interventions assigned to this group

Prospective

Participants enrolled in the prospective group will give a blood sample for immediate DPYD genotyping. Once the results from these tests are in, the treating oncologist have immediate access to the participant's genetic test results and can make dosing decisions/changes to the participant's chemotherapy prescription. The recommended starting doses for 5-FU, capecitabine, tegafur are.

No DPYD-gene variant = normal starting dose (100%)

1 DPYD-gene variant (heterozygous) = Reduced starting dose (50%) Homozygous for 1 DPYD variant or compound heterozygous (>1 variants) = Treatment with 5-FU, capecitabine, tegafur is not recommended .

DPYD genotype

Intervention Type: GENETIC

The SNPs included in this study are the following (dbSNP Reference SNP)

rs3918290(c.1905+1G>A) rs67376798(c.2846A>T) rs55886062(c.1679T>G) rs56038477(75017182)/(c.1236G>A)

Interventions

DPYD genotype

The SNPs included in this study are the following (dbSNP Reference SNP)

rs3918290(c.1905+1G>A) rs67376798(c.2846A>T) rs55886062(c.1679T>G) rs56038477(75017182)/(c.1236G>A)

Intervention Type: GENETIC

Other Intervention Names

Dihydropyrimidine dehydrogenase (DPD) enzyme activity

Eligibility Criteria

Inclusion Criteria

• Patients with cancer that are eligible for systemic treatment with 5-FU, capecitabine, or tegafur.

Exclusion Criteria

• Patients that earlier have been treated with 5-FU, capecitabine, or tegafur

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: lead

Responsible Party

Per Damkier

MD, ph.d. Clinical Professor,

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Per Damkier, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Southern Denmark

Locations

The Department of Oncology at University of southern denmark

Odense, Region Syddanmark, Denmark

Countries

Denmark

Other Identifiers

R231-A14057

Identifier Type: -

Identifier Source: org_study_id