ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12621001117808

Ethics application status

Approved

Date submitted

12/07/2021

Date registered

23/08/2021

Date last updated

23/08/2021

Date data sharing statement initially provided

23/08/2021

Type of registration

Retrospectively registered

Titles & IDs

Public title

Pre-treatment dihydropyrimidine dehydrogenase (DPYD) genotyping in patients receiving fluoropyrimidine (5-Fluorouracil or Capecitabine) chemotherapy: A clinical implementation study of the effect of individualised dosing on treatment related toxicity

Scientific title

Pre-treatment dihydropyrimidine dehydrogenase (DPYD) genotyping to individualise fluoropyrimidine-based chemotherapy: An evaluation of clinical implementation and treatment-related toxicity.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

cancer

Condition category

Condition code

Cancer

Other cancer types

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Pre-treatment dihydropyrimidine dehydrogenase (DPYD) genotyping to individualise fluoropyrimidine-based chemotherapy dosing

All patients receiving fluoropyrimidine chemotherapy for the first time will be offered pre-treatment Sanger DNA sequencing to identify the four DPYD variant genotypes most associated with increased toxicity - single nucleotide polymorphisms c.1905+1G>A (*2A, rs3918290), c.1679T>G (*13, rs55886062), c.2846A>T (rs67376798), and c.1236G>A (rs56038477, E412E, in haplotype B3). Participants will be required to provide a blood sample only.

Those patients with no DPYD variants will proceed receive a 100% dose as planned.

Those patients identified with a single heterozygote DPYD variant will receive a 50% dose reduction for the first two cycles.

For safety reasons, any patients identified as a homozygous genotype or compound heterozygote should not receive fluoropyrimidines and alternative treatment will be recommended. The alternative type of treatment will be at the discretion of the treating Medical Oncologist but may include a different type of chemotherapy such as Raltitrexed.

Results will be checked by the clinician as well as pharmacy and trial coordinators to ensure adherence to the intervention.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Early detection / Screening

Comparator / control treatment

Treatment toxicity compared between those who have a variant and those who don't
For further comparison, a retrospective review will also be undertaken of toxicity rates for all patients who received fluoropyrimidine treatment at the Royal Brisbane and Womens Hospital in 2019.

Control group

Historical

Outcomes

Primary outcome [1]

Incidence of severe treatment related toxicity (CTC grade 3 or higher) within 60 days of a patient beginning fluoropyrimidine treatment.

Timepoint [1]

Within 60 days of beginning treatment

Secondary outcome [1]

Unplanned hospital admissions related to treatment within 60 days of a patient beginning fluoropyrimidine treatment will be reviewed from the patients electronic medical record.

Timepoint [1]

Within 60 days of a patient beginning fluoropyrimidine treatment

Secondary outcome [2]

Rates of fluoropyrimidine dose intensity during the first 60 days of beginning fluoropyrimidine treatment will be reviewed from the patients electronic medical record

Timepoint [2]

At the conclusion of the study

Secondary outcome [3]

Documented practical clinical implementation issues including testing timeframes. This will be assessed via an audit of study records and liaison with Pathology completing the testing.

Timepoint [3]

At the conclusion of the study

Secondary outcome [4]

Rates of fluoropyrimidine dose delays during the first 60 days of beginning fluoropyrimidine treatment will be reviewed from the patients electronic medical record

Timepoint [4]

At the conclusion of the study

Eligibility

Key inclusion criteria

a. Pathologically confirmed malignancy for which treatment with a fluoropyrimidine at full dose (with or without other chemotherapy agents or radiation) is deemed clinically appropriate
b. Adult patient (> 18 years)
c. Receiving their first dose of fluoropyrimidine (either as a single agent or in combination) between 1 July, 2021 and 30 June, 2022.
d. Willing to provide blood sample for pharmacogenetic testing

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

a. Inability to provide informed consent
b. Prior use of fluoropyrimidines
c. Women who are pregnant or breast-feeding
d. Patients with a previously known homozygous polymorphic genotype or compound heterozygous genotype for DPYD.

Study design

Purpose of the study

Prevention

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Nil

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Nil

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety

Statistical methods / analysis

• Prevalence rates of DYPD variants will be summarized as frequency (percent)
• Fluoropyrimidine dose/intensity will be summarized as a mean (percentage) for each different population group.
• Patient and treatment characteristics will be compared between pre and post DYPD testing implementation groups, as well as between those with and without a variant in the post DYPD testing implementation group, using chi-square or Fisher’s exact tests for categorical characteristics and t-tests or Mann-Whitney U tests for continuous characteristics as appropriate.
• For the primary outcome of toxicity experienced within 60 days of beginning fluoropyrimidine and the secondary outcome of having a readmission within 60 days of beginning fluoropyrimidine, univariable binary logistic regression analyses will be performed to observe the effect on these outcomes of pre and post DYPD testing implementation, and potential covariates.
• Covariates with a p-value < 0.2 will be considered further in multivariable logistic regression analyses alongside pre and post DYPD testing implementation groups.
• Covariates will be removed via a variable selection process to obtain a final adjusted model. Cohort will be forced to remain in the model.
• Statistical significance will be indicated at p < 0.05. A similar process will be performed for the comparison between having a variant and no variant in the post DYPD testing implementation group.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

12/07/2021

Date of last participant enrolment

Anticipated

30/06/2022

Actual

Date of last data collection

Anticipated

30/09/2022

Actual

Sample size

Target

280

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [2]

The Prince Charles Hospital - Chermside

Recruitment hospital [3]

North Lakes Health Precinct - North Lakes

Recruitment postcode(s) [1]

4029 - Herston

Recruitment postcode(s) [2]

4032 - Chermside

Recruitment postcode(s) [3]

4509 - North Lakes

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Queensland Health - Metro North Health

Address [1]

Butterfield St, Herston QLD 4019

Country [1]

Australia

Primary sponsor type

Hospital

Name

Queensland Health - Metro North Health

Address

Butterfield St, Herston QLD 4019

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Brisbane & Women's Hospital Human Research Ethics

Ethics committee address [1]

Level 2, Building 34
Royal Brisbane & Women’s Hospital
Butterfield Street, Herston Qld 4029

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/04/2021

Approval date [1]

01/06/2021

Ethics approval number [1]

HREC/2021/QRBW/73708

Summary

Brief summary

This study aims to evaluate the feasibility of pre-treatment DPYD genotyping (a gene that codes for an enzyme that metabolises fluoropyrimidine chemotherapy). For those individuals who have a certain DPYD variant, the study will also aim to assess the safety of reducing their dose of fluoropyrimidine chemotherapy.

Who is it for?
You may be eligible for this study if you are aged 18 years or over and have a confirmed malignancy for which fluoropyrimidine chemotherapy is deemed clinically appropriate.

Study details
Participants will be asked to provide a blood sample for genetic testing. Based on results, individuals may have alterations to their treatment plan such as a 50% dose reduction for the first two cycles of chemotherapy or changes in the drug administered. Data on treatment-related toxicity will be collected.

It is hoped that data from this study will establish the clinical relevance of regular DPYD genotype testing for cancer treatment.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Mark Nalder

Address

Department of Medical Oncology
Cancer Care Services
Royal Brisbane & Women’s Hospital
Herston Qld 4029

Country

Australia

Phone

+61 07 3646 7983

Fax

mark.nalder@health.qld.gov.au

Contact person for public queries

Name

Mark Nalder

Address

Department of Medical Oncology
Cancer Care Services
Royal Brisbane & Women’s Hospital
Herston Qld 4029

Country

Australia

Phone

+61 07 3646 7983

Fax

mark.nalder@health.qld.gov.au

Contact person for scientific queries

Name

Mark Nalder

Address

Department of Medical Oncology
Cancer Care Services
Royal Brisbane & Women’s Hospital
Herston Qld 4029

Country

Australia

Phone

+61 07 3646 7983

Fax

mark.nalder@health.qld.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Ethical approval.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
12509	Study protocol					381432-(Uploaded-12-07-2021-09-31-20)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically