Pharmacogenomics for Better Treatment of Fungal Infections in Cancer

NCT ID: NCT06510699

Last Updated: 2025-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-14

Study Completion Date

2026-09-02

Brief Summary

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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.

Detailed Description

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Participants will be randomly assigned to standard care or precision care. Current standard of care at trial-site institutions uses weight-based (mg/kg) initial dosing of voriconazole, with dose adjustment based on standard therapeutic drug monitoring (TDM) results of measured voriconazole concentrations based on clinical judgement. In precision care, voriconazole dosing will be initiated using current standard dosing. Samples for the TDM and genotype testing will be collected. Based on results of these tests on Day 5 (+/- 1 day) patients will be evaluated for dose adjustment using dosing software that includes patient data, TDM and genotype data.

Trial procedures: following baseline data collection and randomisation genotype testing will be performed on Day 1. The precision care group have dose adjustment performed on Days 5, 9, 15, and 22 using genotype and/or TDM results in dosing software. The standard care group will have TDM performed, and dose adjustments in accordance with usual clinical practice. Blood sampling for TDM will be performed 24-hours prior to dose adjustment, with additional blood samples collected on Days 1 and 2 in both standard care and precision care groups. All blood sampling, genotype testing and dose adjustments will be performed +/- day to support feasibility.

The primary objective is to compare the proportion of patients achieving therapeutic voriconazole exposure at Day 8 when using precision care compared to standard care.

Secondary objectives are:

1. Clinical: comparison of clinical success of voriconazole treatment between precision care and standard care groups, where clinical success is defined as an absence of clinical deterioration or event that requires a change of therapy.
2. Antifungal exposure: to compare antifungal exposure over the first 28 days of therapy between precision care and standard care groups.
3. Comparative precision care methodologies: compare if there is a difference in daily dose recommendations between using a genotype nomogram, dosing software with TDM, or a combination of dose adjustment in precision care.
4. Feasibility of precision care interventions: to determine if it is feasible to perform the measurement of voriconazole concentrations and genotype testing for use in dosing software in time to intervene prior to Day 5 and/or Day 9 dose adjustment.
5. Genotype: describe clinical success of voriconazole between genotypes.

The implementation feasibility sub-study will assess the scalability of precision care to support optimal voriconazole dosing by tailoring the intervention to each trial setting and measuring outcomes with the involvement of key stakeholders (end-users, health administrators, consumers, community members).

Data will be collected to ascertain Fidelity including: 1) assess barriers and enablers; 2) identify prioritise the factors influencing delivery and tailor these to fit local settings; 3) assess intended fidelity to the precision care intervention.

Data will be collected to ascertain Feasibility or the extent to which precision care can be successfully used in each study setting via completion of the feasibility implementation measure (FIM) at baselines and quarterly thereafter, including qualitative interviews at the end of the study.

Data will be collected to ascertain Acceptability or whether end-users perceive precision care as agreeable or satisfactory by survey and qualitative interviews with pharmacists, physicians and health administrators.

Data will be collected to undertake an economic evaluation to determine the cost-effectiveness of precision versus standard care, exploring individual level data, incremental cost effectiveness ratios (ICERs) at day 14 and 30; and cost-utility analysis to demonstrate if precision care offers value for money at Day 30 in the Australian setting. The health economic evaluation will include use of surveys to capture: 1) healthcare usage of trial participants; 2) implementation feasibility measures; and 3) implementation costs.

Data will be collected to ascertain scalability or the ability to expand the efficacy of precision care on a small scale in controlled conditions to real world conditions to a greater proportion of the population.

Therapeutic trough voriconazole exposures (concentrations) In this trial, serum concentrations \> 1 mg/L (minimum effective concentration) and \< 5 mg/L (maximum safe concentration) are defined as the therapeutic range. Treating clinicians may nominate an individualised patient target within this range prior to randomisation and that range will be applied during the trial. Where dosing software is being applied, the software will be programmed to target 2.5 mg/L.

Conditions

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Fungal Infection Haematological Malignancy Blood Cancer Infectious Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

PRAGMATIC is a parallel-group randomised (1:1) clinical trial aiming to recruit at least 104 patients. A hybrid feasibility sub-study will assess the scalability of genotype directed dosing to ensure a 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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Precision Care

Voriconazole dosing will be initiated using current standard care dosing. Samples for TDM and genotype testing will be collected. Based on the results of these tests on Day 5, 8, 14, and up to day 30 ( ± 1 day) patients will be evaluated for dose adjustment using dosing software that includes patient data including TDM and genotype data.

Group Type EXPERIMENTAL

genotype-directed dosing with dosing software based on therapeutic drug monitoring

Intervention Type OTHER

Genotype-directed dosing with dosing software based on therapeutic drug monitoring

Standard Care

Current standard of care at trial-site institutions uses weight-based (mg/kg) initial dosing of voriconazole, with dose adjustment based on standard therapeutic drug monitoring (TDM) results of measured voriconazole concentrations and based on clinical judgement.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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genotype-directed dosing with dosing software based on therapeutic drug monitoring

Genotype-directed dosing with dosing software based on therapeutic drug monitoring

Intervention Type OTHER

Other Intervention Names

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genotype directed with dosing software

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 2 years.
* Written informed consent obtained.
* Decision to prescribe voriconazole.
* Diagnosed with haematological malignancy or disorder.
* Admitted to a trial site, or sufficient outpatient follow-up appointments are feasible

Exclusion Criteria

* Post-allogeneic haematopoietic stem cell transplant (HCT) patient, without access to pre HCT DNA
* Death is likely imminent within 7 days.
* Previously randomised to this trial
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Metro North Hospital and Health Service

UNKNOWN

Sponsor Role collaborator

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

OTHER

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role collaborator

Western Sydney Local Health District

OTHER

Sponsor Role collaborator

Sydney Children's Hospitals Network

OTHER

Sponsor Role collaborator

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role collaborator

University of Melbourne

OTHER

Sponsor Role collaborator

Royal Adelaide Hospital

OTHER

Sponsor Role collaborator

Pathology Queensland

UNKNOWN

Sponsor Role collaborator

Royal Brisbane and Women's Hospital

OTHER_GOV

Sponsor Role collaborator

Lady Cilento Children's Hospital, Brisbane

OTHER

Sponsor Role collaborator

The University of Queensland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jason A Roberts, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Queensland

Locations

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Fred Hutchinson Cancer Centre

Seattle, Washington, United States

Site Status RECRUITING

Sydney Children's Hospital Network

Sydney, New South Wales, Australia

Site Status RECRUITING

Westmead Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia

Site Status RECRUITING

Children's Hospital Queensland

South Brisbane, Queensland, Australia

Site Status RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Countries

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United States Australia

Central Contacts

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Jason A Roberts, PhD

Role: CONTACT

+61 7 3346 5032 ext. 65032

Luminita Vlad

Role: CONTACT

61 7 3346 5045

Facility Contacts

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Ashleigh Miller

Role: primary

206-667-1994

Catherine Professor Liu, MD

Role: backup

206-667-2729

Tony Lai

Role: primary

+61 2 9845 2700

Shirley Wong

Role: backup

Johannes Alffenaar

Role: primary

+61 2 8627 0019

Catherine Linh

Role: backup

Midori Nakagaki, PhD

Role: primary

+61 7 3647 0185

Amy Legg

Role: backup

+61 7 3647 0802

Adam D Irwin, MBBS, PhD

Role: primary

07 3346 5075

Rachael Lawson, PhD

Role: backup

Philip R Selby

Role: primary

08 7074 0000

Jane Rose

Role: backup

Monica Slavin, MBBS, FRACP, MD, FAAHMS, FECMM

Role: primary

+61 3 8559 5000

Rachel Wolstencroft

Role: backup

+61 3 8559 7973

Other Identifiers

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PRAGMATIC 01

Identifier Type: -

Identifier Source: org_study_id

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