Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001301651
Ethics application status
Approved
Date submitted
10/11/2023
Date registered
13/12/2023
Date last updated
23/02/2024
Date data sharing statement initially provided
13/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
GeneScreen 5-FU: DPYD Genotype-guided dose Personalisation for Fluoropyrimidine prescribing in Solid Organ Cancer Patients
Scientific title
GeneScreen 5-FU: DPYD Genotype-guided dose Personalisation for Fluoropyrimidine prescribing in Solid Organ Cancer Patients
Secondary ID [1] 307487 0
none
Universal Trial Number (UTN)
Trial acronym
GeneScreen 5-FU
Linked study record
ACTRN12622000963729. Pilot study for current large scale project

Health condition
Health condition(s) or problem(s) studied:
Cancer 331701 0
Fluoropyrimidine chemotherapy toxicity 331702 0
DPD deficiency 332196 0
DPYD gene variant 332197 0
UGT1A1 gene variant 332198 0
Condition category
Condition code
Cancer 328438 328438 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single arm interventional prospective study.
Patients with solid organ cancers undergo pharmacogenomic (PGx) genotyping to identify dihydropyrimidine dehydrogenase (DPYD) and UDP glucuronosyltransferase family 1 (UGT1A1) variants prior to commencing Fluoropyrimidine (FP) and Irinotecan (IRI) (where applicable) chemotherapies. All possible FP and IRI chemotherapy regimens are accepted (regardless of dosing and dose intervals). Both intravenous and oral FP regimens are included.

Genotype status is determined by blood test to be taken prior to commencing chemotherapy.This can be taken at any time prior to commencement of treatment, but sooner is better to allow adequate laboratory processing time. Typical turn around is 5 business days.
Patients found to have a DPYD variant undergo an FP dose reduction (as per international guidelines) to reduce toxicity and improve tolerability. No other alterations to dose interval or regimen are expected. Patients will be monitored for 60 days post first exposure via routine clinic visits, and chemotherapy related toxicities will be recorded.

UGT1A1 genotyping is for feasibility analysis only, IRI dose adjustments to be made at clinician discretion.
Intervention code [1] 327254 0
Early detection / Screening
Comparator / control treatment
Historical data collected from audit of 500 patients who undertook FP chemotherapy without genotyping from June 2020 to June 2022 in Hunter New England Local Health District
Control group
Historical

Outcomes
Primary outcome [1] 336401 0
FP toxicity, assessed by CTCAE v5 criteria at routine visits post first exposure, or during hospitalisations in between routine visits
Timepoint [1] 336401 0
Up to 60 days post first exposure to FP chemotherapy
Primary outcome [2] 336403 0
Cost effectiveness: health economic modelling and development of decision analytic model. Data to be collected from hospital financial records with data-linkage to the Pharmaceutical Benefits Scheme database to determine treatment costs
Timepoint [2] 336403 0
immediately following collection of patient dataset
Secondary outcome [1] 428176 0
DPYD frequency in Australian population (carriers as a proportion of total study cohort)
Timepoint [1] 428176 0
From baseline blood test
Secondary outcome [2] 428793 0
UGT1A1 feasibility: assessed as the turn around time for testing from the provision of sample to the return of results as recorded in a study-specific database
Timepoint [2] 428793 0
Cumulative data assessed at the conclusion of the study
Secondary outcome [3] 429544 0
Development of metastatic disease
Timepoint [3] 429544 0
Review of medical records from start of trial to 5 years post first chemotherapy
Secondary outcome [4] 429545 0
Disease free survival
Timepoint [4] 429545 0
Review of medical records from start of trial to 5 years post first chemotherapy
Secondary outcome [5] 429546 0
Progression free survival
Timepoint [5] 429546 0
Review of medical records from start of trial to 5 years post first chemotherapy
Secondary outcome [6] 429547 0
Overall survival
Timepoint [6] 429547 0
Review of medical records from start of trial to 5 years post first chemotherapy

Eligibility
Key inclusion criteria
Minimum 18 years old
Solid organ malignancy requiring fluoropyrimidine chemotherapy (+/- irinotecan for UGT1A1 genotyping)
Able to provide informed consent
Able to provide blood sample
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior fluoropyrimidine exposure
Pregnant or breastfeeding women
Unwilling to provide consent and/ or blood sample

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Historical data collected from audit of 500 patients who undertook FP chemotherapy without genotyping from June 2020 to June 2022 in Hunter New England Local Health District
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
29/02/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
5000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA

Funding & Sponsors
Funding source category [1] 311767 0
Government body
Name [1] 311767 0
National Health and Medical Research Council
Country [1] 311767 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Hunter Medical Research Unit
Address
1 Kookaburra Cct, New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 313227 0
University
Name [1] 313227 0
University of Newcastle
Address [1] 313227 0
University Dr, Callaghan NSW 2308
Country [1] 313227 0
Australia
Secondary sponsor category [2] 317113 0
University
Name [2] 317113 0
University of Adelaide
Address [2] 317113 0
University of Adelaide, Adelaide, SA 5005
Country [2] 317113 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311208 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 311208 0
John Hunter Hospital, Lookout Rd, New Lambton Heights NSW 2305
Ethics committee country [1] 311208 0
Australia
Date submitted for ethics approval [1] 311208 0
14/06/2023
Approval date [1] 311208 0
21/09/2023
Ethics approval number [1] 311208 0
2023/ETH01211: GeneScreen 5FU: prospective genotype-guided dose personalisation study for patients with solid organ malignancy

Summary
Brief summary
This study aims to identify the optimal way to implement fluoropyrimidine chemotherapy in patients who have a genetic variant of the DPYD gene, the ability to test for UGT1A1 prior to irinotecan chemotherapy, and cost effectiveness of a large-scale roll out of this screening program.

Who is it for?

You may be eligible to join this study if you are aged 18 or over, and have solid organ malignancy requiring fluoropyrimidine chemotherapy. You may be eligible for additional for UGT1A1 genotyping if you require irinotecan chemotherapy

Study details

All participants who meet the eligibility criteria in this study will undergo pharmacogenomic (PGx) genotyping to identify DPYD and UGT1A1 variants prior to commencing Fluoropyrimidine (FP) and Irinotecan (IRI)(where applicable) chemotherapies. Genotyping is conducted from a blood sample collected from patients prior to commencing chemotherapy, and relevant adjustments to chemotherapy dosing is made in accordance with international dosing guidelines.

Participants will be followed for 60 days to assess for acute chemotherapy induced toxicity, and beyond completion of chemotherapy regimen to assess cost-effectiveness and feasibility of the screening program. No additional tests will be required from patients beyond standard of care.

It is hoped that this research project will determine the feasibility of DPYD genetic testing for cancer patients which may assist with providing personalised treatment options for these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120334 0
Prof Rodney Scott
Address 120334 0
Hunter Medical Research Institute, Lot 1 Kookaburra Cct, New Lambton Heights NSW 2305
Country 120334 0
Australia
Phone 120334 0
+61409926764
Fax 120334 0
Email 120334 0
rodney.scott@newcastle.edu.au
Contact person for public queries
Name 120335 0
Ms Ann Thomas
Address 120335 0
Hunter Medical Research Institute, Lot 1 Kookaburra Cct, New Lambton Heights NSW 2305
Country 120335 0
Australia
Phone 120335 0
+61432330959
Fax 120335 0
Email 120335 0
ann.thomas@newcastle.edu.au
Contact person for scientific queries
Name 120336 0
Dr Cassandra White
Address 120336 0
Hunter Medical Research Institute, Lot 1 Kookaburra Cct, New Lambton Heights NSW 2305
Country 120336 0
Australia
Phone 120336 0
+61240420000
Fax 120336 0
Email 120336 0
cassandra.white10@uon.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
de-identified data
When will data be available (start and end dates)?
following publication, no end date
Available to whom?
researchers who provide a sound proposal
Available for what types of analyses?
IPD meta analyses
How or where can data be obtained?
by emailing the principal investigator (rodney.scott@newcastle.edu.au). Supporting documents can be requested vis this email.


What supporting documents are/will be available?

No Supporting Document Provided



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.