NeoplasmsDPYD-NOWNCT04300361
Identifying Novel Variants in the DPYD Gene in Patients of Non-Western Descent
An observational study of Neoplasms, run by Leiden University Medical Center.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Sequencing of DPYD gene
- How many people
- 600 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2020to 1 Aug 2022
- 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: 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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Prospective, Multicenter, Observational Study to Identify Novel Deleterious Variants in the DPYD Gene in Patients of Non-Western Descent: The DPYD-NOW Study
This is a observational, multicenter study to identify novel variants of the DPYD gene which are possible deleterious in patients of non-Western descent.
Read the detailed description
Research has shown that DPYD-guided dose-individualization based on 4 DPYD variants (DPYD*2A, c.1236G>A, c.2846A>T and c.1679T>G) can significantly reduce severe fluoropyrimidine-related toxicity. However, these 4 variants are most likely not predictive for toxicity in patients of non-Western descent. In this study the DPYD gene of patients of non-Western descent will be sequenced to identify novel variants that could be associated with a reduced DPD enzyme activity and an increased risk of developing severe fluoropyrimdine-related toxicity. Additionally, the ability to predict if a DPYD variant is possibly deleterious by a recombinant model systen (DPYD-varifier) will be studied.
- Conditions
- Neoplasms
- Being tested
- Sequencing of DPYD gene
- Keywords
- Fluoropyrimidines, DPYD, Genotyping, Capecitabine, 5-Fluorouracil, 5-FU, Non-Western
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sequencing of DPYD geneGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: Sequencing of DPYD gene |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: Through study completion, an average of 2 years
Ability of the DPYD-varifier to predict if a novel DPYD variant is deleterious
Measured: Through study completion, an average of 2 years
Frequency of DPYD variants per ethnic origin
Measured: Through study completion, an average of 2 years
Correlation between genetic variants in genes other than DPYD and fluoropyrimidine-related toxicity
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2020
- Study start1 Mar 2020 (estimated)
- Primary completion1 Mar 2022 (estimated)
- Study completion1 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Netherlands Cancer Institute, Erasmus Medical Center, Haga Hospital, Medical Center Haaglanden
- Responsible party
- Principal investigator, HansGelderblom, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04300361
- Sponsor's protocol ID
- DPNOW
- Acronym
- DPYD-NOW
- Status last verified
- Mar 2020
- First submitted
- 24 Feb 2020
- Last updated
- 9 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Observational Study to Identify Novel Deleterious Variants in the DPYD Gene in Patients of Non-Western Descent: The DPYD-NOW Study
- ClinicalTrials.gov ID
- NCT04300361
- Acronym / sponsor ID
- DPYD-NOW / DPNOW
- Conditions
- Neoplasms
- Keywords
- Fluoropyrimidines, DPYD, Genotyping, Capecitabine, 5-Fluorouracil, 5-FU, Non-Western
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- The Netherlands Cancer Institute, Erasmus Medical Center, Haga Hospital, Medical Center Haaglanden
- Study start
- 1 Mar 2020 (estimated)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 1 Aug 2022 (estimated)
- First posted
- 9 Mar 2020 (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.
This is a observational, multicenter study to identify novel variants of the DPYD gene which are possible deleterious in patients of non-Western descent.
Detailed description
Research has shown that DPYD-guided dose-individualization based on 4 DPYD variants (DPYD*2A, c.1236G>A, c.2846A>T and c.1679T>G) can significantly reduce severe fluoropyrimidine-related toxicity. However, these 4 variants are most likely not predictive for toxicity in patients of non-Western descent. In this study the DPYD gene of patients of non-Western descent will be sequenced to identify novel variants that could be associated with a reduced DPD enzyme activity and an increased risk of developing severe fluoropyrimdine-related toxicity. Additionally, the ability to predict if a DPYD variant is possibly deleterious by a recombinant model systen (DPYD-varifier) will be studied.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Non-Western patients | – | Genetic: Sequencing of DPYD genePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (2 listed)
- 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
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 |
|---|---|---|
| Sequencing of DPYD geneThe 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. | Genetic | Non-Western patients |
Primary outcome
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
Time frame: Patients will be followed for the first 2 cycles (each cycle is 28 days).
4 secondary outcomes
DPD enzyme activity of patients carrying a novel DPYD variant compared to wildtype patients measured in peripheral blood mononuclear cells (PBMCs)
Time frame: Through study completion, an average of 2 years
Ability of the DPYD-varifier to predict if a novel DPYD variant is deleterious
Time frame: Through study completion, an average of 2 years
Frequency of DPYD variants per ethnic origin
Time frame: Through study completion, an average of 2 years
Correlation between genetic variants in genes other than DPYD and fluoropyrimidine-related toxicity
Time frame: Through study completion, an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- 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.
Questions about this trial
What is this clinical trial studying?
An observational study of Neoplasms, run by Leiden University Medical Center.
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 8 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hans Gelderblom, Prof. (+31 (0)71 - 526 9111, a.j.gelderblom@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Patients will be followed for the first 2 cycles (each cycle is 28 days).). 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 9 Mar 2020.