None listed
Conditions
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.
Interventions
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)
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.
Sponsors
Queensland Health - Metro North Health
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
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.
Outcome results
None listed