Trial Title:
Pharmacogenomics for Better Treatment of Fungal Infections in Cancer
NCT ID:
NCT06510699
Condition:
Fungal Infection
Haematological Malignancy
Blood Cancer
Infectious Disease
Conditions: Official terms:
Infections
Communicable Diseases
Mycoses
Neoplasms
Hematologic Neoplasms
Conditions: Keywords:
infection
cancer
pharmacogenomic
genotype-based dosing
CYP2C19
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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 purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
genotype-directed dosing with dosing software based on therapeutic drug monitoring
Description:
Genotype-directed dosing with dosing software based on therapeutic drug monitoring
Arm group label:
Precision Care
Other name:
genotype directed with dosing software
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
2 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutchinson Cancer Centre
Address:
City:
Seattle
Zip:
908109-1024
Country:
United States
Contact:
Last name:
Julian Lindsay
Phone:
206-667-6274
Email:
jlindsay@fredhutch.org
Facility:
Name:
Sydney Children's Hospital Network
Address:
City:
Sydney
Zip:
21452031
Country:
Australia
Contact:
Last name:
Tony Lai
Phone:
+61 2 9845 2700
Email:
tony.lai@health.nsw.gov.au
Contact backup:
Last name:
Shirley Wong
Email:
shirley.wong@health.nsw.gov.au
Facility:
Name:
Westmead Hospital
Address:
City:
Sydney
Zip:
2145
Country:
Australia
Contact:
Last name:
Johannes Alffenaar
Phone:
+61 2 8627 0019
Email:
johannes.alffenaar@sydney.edu.au
Facility:
Name:
Royal Brisbane & Women's Hospital
Address:
City:
Brisbane
Zip:
4029
Country:
Australia
Contact:
Last name:
Midori Nakagaki
Phone:
+61 7 3647 0185
Email:
midori.nakagaki@health.qld.gov.au
Contact backup:
Last name:
Amy Legg
Phone:
+61 7 3647 0802
Email:
amy.legg@health.qld.gov.au
Facility:
Name:
Children's Hospital Queensland
Address:
City:
South Brisbane
Zip:
4029
Country:
Australia
Contact:
Last name:
Adam D Irwin
Phone:
07 3346 5075
Email:
a.irwin@uq.edu.au
Contact backup:
Last name:
Sophie Anderson-James
Email:
sophie.anderson-james@health.qld.gov.au
Facility:
Name:
Royal Adelaide Hospital
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Contact:
Last name:
Philip R Selby
Phone:
08 7074 0000
Email:
philip.selby@sa.gov.au
Contact backup:
Last name:
Jane Rose
Email:
Jane.rose@sa.gov.au
Facility:
Name:
Peter MacCallum Cancer Centre
Address:
City:
Melbourne
Zip:
3053
Country:
Australia
Contact:
Last name:
Monica Slavin
Phone:
+61 3 8559 5000
Email:
monica.slavin@petermac.org
Contact backup:
Last name:
Rachel Wolstencroft
Phone:
+61 3 8559 7973
Email:
infectiousdiseases.clinicaltrials@petermac.org
Start date:
November 1, 2024
Completion date:
September 2, 2026
Lead sponsor:
Agency:
The University of Queensland
Agency class:
Other
Collaborator:
Agency:
Metro North Hospital and Health Service
Agency class:
Other
Collaborator:
Agency:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Agency class:
Other
Collaborator:
Agency:
University of Sydney
Agency class:
Other
Collaborator:
Agency:
Western Sydney Local Health District
Agency class:
Other
Collaborator:
Agency:
Sydney Children's Hospitals Network
Agency class:
Other
Collaborator:
Agency:
Peter MacCallum Cancer Centre, Australia
Agency class:
Other
Collaborator:
Agency:
University of Melbourne
Agency class:
Other
Collaborator:
Agency:
Queensland Children's Hospital
Agency class:
Other
Collaborator:
Agency:
Royal Adelaide Hospital
Agency class:
Other
Collaborator:
Agency:
Pathology Queensland
Agency class:
Other
Collaborator:
Agency:
Royal Brisbane and Women's Hospital
Agency class:
Other
Source:
The University of Queensland
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06510699
