Adverse Drug EventNCT05266300
Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines.
An observational study of Adverse Drug Event and Colon Cancer, run by University of Southern Denmark at 1 site in Denmark.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adverse Drug Event, Colon Cancer, Breast Cancer
- What is being tested?
- DPYD genotype
- How many people
- 722 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2020to 1 Oct 2022
- How long will I take part?
- 6 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cancer patients treated at The Department of Oncology at Odense University Hospital (OUH)
Who may be able to join
- Patients with cancer that are eligible for systemic treatment with 5-FU, capecitabine, or tegafur.
Who cannot join
- Patients that earlier have been treated with 5-FU, capecitabine, or tegafur
Trial locations and contacts
1 site in 1 country.
Denmark1 site
The Department of Oncology at University of southern denmark
Odense, Region Syddanmark, 5000
About this study
Official title: Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines
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).
Read the 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
- Being tested
- DPYD genotype
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions, Colonic Neoplasms, Breast Neoplasms, Pancreatic Neoplasms, Rectal Neoplasms, Stomach Neoplasms, Esophageal Neoplasms, Bile Duct Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DPYD genotypeGenetic
Also called Dihydropyrimidine dehydrogenase (DPD) enzyme activity
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| 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 . Receives: Genetic: DPYD genotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Rate of grade 3-5 adverse events (CTCAE) Version 5.0
Measured: Up to 6 months
Secondary outcomes (6)
5-FU or capecitabine or S1-related mortality, all patients
Rate of mortality related to adverse drug reaction
Measured: Up to 6 months
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.
Measured: Up to 6 months
Overall mortality, all patients
Rate of mortality in all patients
Measured: Up to 6 months
Overall mortality, DPYD variant carriers
Rate of mortality in patients with DPYD-variants.
Measured: Up to 6 months
Length of hospital stay
Number of days participants is admitted to the hospital.
Measured: Up to 6 months
Rate of discontinuation of fluoropyrimidines due to adverse events
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2022
- Study start1 Sep 2020
- Primary completion1 Jun 2022
- Study completion1 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adverse Drug EventStudies of the same condition, open and under way.
- More trials run by University of Southern DenmarkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 722 participants (actual)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- University of Southern Denmark
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital
- Responsible party
- Principal investigator, Per Damkier, University of Southern Denmark
- Investigators
- Per Damkier, MD, PhD, Principal investigator, University of Southern Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05266300
- Sponsor's protocol ID
- R231-A14057
- Status last verified
- Oct 2022
- First submitted
- 16 Dec 2021
- Last updated
- 1 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines
- ClinicalTrials.gov ID
- NCT05266300
- Acronym / sponsor ID
- R231-A14057
- Conditions
- Adverse Drug Event, Colon Cancer, Breast Cancer, Pancreas Cancer, Rectal Cancer, Gastric Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 722 participants (actual)
- Lead sponsor
- University of Southern DenmarkUniversity, hospital or other
- Collaborators
- Odense University Hospital
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 4 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
| Prospective | – | Genetic: DPYD genotypeParticipants 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 . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cancer patients treated at The Department of Oncology at Odense University Hospital (OUH)
Key inclusion criteria (1 listed)
- Patients with cancer that are eligible for systemic treatment with 5-FU, capecitabine, or tegafur.
Key exclusion criteria (1 listed)
- Patients that earlier have been treated with 5-FU, capecitabine, or tegafur
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DPYD genotypeAlso: Dihydropyrimidine dehydrogenase (DPD) enzyme activityThe 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) | Genetic | Prospective |
Primary outcome
Adverse events
Time frame: Up to 6 months
Rate of grade 3-5 adverse events (CTCAE) Version 5.0
6 secondary outcomes
5-FU or capecitabine or S1-related mortality, all patients
Time frame: Up to 6 months
5-FU or capecitabine or S1-related mortality, DPYD variant carriers
Time frame: Up to 6 months
Overall mortality, all patients
Time frame: Up to 6 months
Overall mortality, DPYD variant carriers
Time frame: Up to 6 months
Length of hospital stay
Time frame: Up to 6 months
Rate of discontinuation of fluoropyrimidines due to adverse events
Time frame: Up to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Damkier, MD, PhD principal investigator
University of Southern Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adverse Drug Event and Colon Cancer, run by University of Southern Denmark at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2022; AzTrials last refreshed its copy on 7 Nov 2026.