Clinical trial NCT05266300: Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines.
Official title: Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adverse Drug Event
Colon Cancer
Breast Cancer
Pancreas Cancer
Rectal Cancer
Gastric Cancer
Oesophageal Cancer
Bile Duct Cancer
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2022-03-04
Enrollment: 722
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer patients treated at The Department of Oncology at Odense University Hospital (OUH)

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.

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

Primary outcomes:
measure: Adverse events
timeFrame: Up to 6 months
Secondary outcomes:
measure: 5-FU or capecitabine or S1-related mortality, all patients
timeFrame: Up to 6 months
measure: 5-FU or capecitabine or S1-related mortality, DPYD variant carriers
timeFrame: Up to 6 months
measure: Overall mortality, all patients
timeFrame: Up to 6 months
measure: Overall mortality, DPYD variant carriers
timeFrame: Up to 6 months
measure: Length of hospital stay
timeFrame: Up to 6 months
measure: Rate of discontinuation of fluoropyrimidines due to adverse events
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: The Department of Oncology at University of southern denmark
state: Syddanmark
Study officials:
affiliation: University of Southern Denmark
name: Per Damkier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: