Pharmacogenomics for Better Treatment of Fungal Infections in Cancer
NCT Number: NCT06510699
Acronym: PRAGMATIC
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Fungal Infection|Haematological Malignancy|Blood Cancer|Infectious Disease
Interventions: OTHER: genotype-directed dosing with dosing software based on therapeutic drug monitoring
Sponsor: The University of Queensland
Collaborators: Metro North Hospital and Health Service|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|University of Sydney|Western Sydney Local Health District|Sydney Children's Hospitals Network|Peter MacCallum Cancer Centre, Australia|University of Melbourne|Queensland Children's Hospital|Royal Adelaide Hospital|Pathology Queensland|Royal Brisbane and Women's Hospital
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 104
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-11-01
Completion Date: 2026-09-02
Locations: Fred Hutchinson Cancer Centre, Seattle, Washington, 908109-1024, United States|Sydney Children's Hospital Network, Sydney, New South Wales, 21452031, Australia|Westmead Hospital, Sydney, New South Wales, 2145, Australia|Royal Brisbane & Women's Hospital, Brisbane, Queensland, 4029, Australia|Children's Hospital Queensland, South Brisbane, Queensland, 4029, Australia|Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia|Peter MacCallum Cancer Centre, Melbourne, Victoria, 3053, Australia

Summary:
This project aims to address invasive fungal infections in patients with blood cancer, by precision dosing of voriconazole based on CYP2C19 genotype testing with Bayesian dose-forecasting dosing software to develop patient-centric and maximally effective dosing regimens. This study investigates if voriconazole increases the proportion of patients achieving therapeutic exposure at day 8 of dosing compared with standard care; and will assess factors that influence the implementation of genotype testing and dosing software in the healthcare system, including fidelity, feasibility, acceptability and cost-effectiveness. It will recruit at least 104 kids and adults in a parallel-group randomised clinical trial. A hybrid feasibility sub-study will assess the scalability of genotype-directed dosing to ensure sustainable integration of the interventions into the clinical workflow. A health economic sub-study will evaluate the costs, health outcomes and cost-effectiveness of genotype-directed testing compared to standard care.

Primary Outcome Measures: Therapeutic trough voriconazole concentration at Day 8, Proportion of patients with measured therapeutic trough voriconazole concentration at Day 9 (+/- 1 day), Day 8
Secondary Outcome Measures: Simulated therapeutic trough voriconazole exposure at Day 8, Proportion of patients with simulated therapeutic trough voriconazole exposure at Day 8, Day 8|Measured therapeutic trough voriconazole exposure at Day 14., Proportion of patients with measured therapeutic trough voriconazole exposure at Day 14., Day 14|Simulated therapeutic trough voriconazole exposure at Day 14, Proportion of patients with simulated therapeutic trough voriconazole exposure at Day 14, Day 14|Measured therapeutic trough voriconazole exposure at both Days 8 and 14, Proportion of patients with measured therapeutic trough voriconazole exposure at both Days 8 and 14, Days 8 and 14|Simulated therapeutic trough voriconazole exposure at both Days 8 and 14, Proportion of patients with simulated therapeutic trough voriconazole exposure at both Days 8 and 14, Days 8 and 14|Simulated therapeutic trough voriconazole exposure from Day 8 to Day 30, Proportion of patients with simulated therapeutic trough voriconazole exposure from Day 8 to Day 30, Day 8 to Day 30|Days to achieve first measured therapeutic trough voriconazole exposure, Number of days to achieve first measured therapeutic trough voriconazole exposure, Assessed over 30 days|Doses to achieve first measured therapeutic trough voriconazole exposure., Number of doses to achieve first measured therapeutic trough voriconazole exposure., Assessed over 30 days|Percent difference in dose when dose adjustment is performed, Percent difference in dose when dose adjustment is performed (i) on the first occasion and (ii) on subsequent occasions (set to 0 if no adjustment)., Assessed over 30 days|Number of days of antifungal therapy, Number of days of antifungal therapy, Assessed over 30 days|Number of doses of antifungal therapy, Number of doses of antifungal therapy, Assessed over 30 days|Clinical cure or stable disease, Proportion of patients achieving invasive fungal disease (IFD) clinical cure or stable disease; defined by treating team, if indication is IFD treatment, Assessed over 30 days|Patients with no reported fungal infection during course, Proportion of patients with no reported fungal infection during course, if indication is IFD prophylaxis., Assessed over 30 days|Hospital free days, Number of hospital free days at day 30, Day 30|Length of hospital stay post-randomisation, Length of hospital stay post-randomisation, Assessed over 30 days|Number of patients experiencing at least one adverse event, Number of patients experiencing at least one adverse event, Assessed over 30 days|Number and type of adverse events, Number and type of adverse events, Assessed over 30 days|All-cause mortality at 30 days, All-cause mortality at 30 days, Assessed over 30 days|Clinical success, Proportion of patients achieving clinical success, defined as an absence of a clinical deterioration or event that requires a change of therapy, Assessed over 30 days