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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05266300
• Other study ID #: R231-A14057
• Status: Completed
• Start date: September 1, 2020
• Est. completion date: October 1, 2022

Study information

• Verified date: October 2022
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 722
• Est. completion date: October 1, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adverse Drug Event
• Bile Duct Cancer
• Bile Duct Neoplasms
• Breast Cancer
• Cholangiocarcinoma
• Colon Cancer
• Drug-Related Side Effects and Adverse Reactions
• Gastric Cancer
• Oesophageal Cancer
• Pancreas Cancer
• Pancreatic Neoplasms
• Rectal Cancer

Intervention

Genetic:
• 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)

Locations

Country	Name	City	State
Denmark	The Department of Oncology at University of southern denmark	Odense	Syddanmark

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern Denmark	Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Rate of grade 3-5 adverse events (CTCAE) Version 5.0	Up to 6 months
Secondary	5-FU or capecitabine or S1-related mortality, all patients	Rate of mortality related to adverse drug reaction	Up to 6 months
Secondary	5-FU or capecitabine or S1-related mortality, DPYD variant carriers	Rate of mortality related to adverse drug reactions in patients with a DPYD gene variant.	Up to 6 months
Secondary	Overall mortality, all patients	Rate of mortality in all patients	Up to 6 months
Secondary	Overall mortality, DPYD variant carriers	Rate of mortality in patients with DPYD-variants.	Up to 6 months
Secondary	Length of hospital stay	Number of days participants is admitted to the hospital.	Up to 6 months
Secondary	Rate of discontinuation of fluoropyrimidines due to adverse events		Up to 6 months