Clinical trial NCT05667766: Minimising Adverse Drug Reactions and Verifying Economic Legitimacy in Children (MARVEL-PIC)
Official title: Minimising Adverse Drug Reactions and Verifying Economic Legitimacy - Pharmacogenomics Implementation in Children (MARVEL-PIC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neoplasms
Bone Marrow Transplantation
Keywords: cancer
paediatric
pharmacogenomic
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2022-12-29
Enrollment: 880
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: A prospective, open, randomised implementation study in paediatric cancer patients. The study aims to determine whether a personalised approach will result in an overall reduction in clinically relevant adverse drug reactions (ADRs) and to evaluate the economic and quality of life impacts. Participants will be randomised to receive personalised guided prescribing of supportive care therapy (study arm) or standard of care (control arm) for a period of 12 weeks. The follow up period includes prospective patient reporting of symptoms and quality of life through electronically delivered surveys, for a maximum of 12 months.

Detailed description: One of the main areas of precision medicine that is easily implementable is pharmacogenomic testing. Germline testing of genes predisposing to drug toxicity or inefficacy can inform drug selection and dosing. This steers away from the historical 'trial and error' approach, avoids unnecessary adverse drug reactions (ADRs) and can potentially impact on health economic savings, through reduction in readmissions and admissions with ADRs.

This study will be a prospective, open, randomised implementation study in paediatric and adolescent patients with a new diagnosis of cancer or who are proceeding to first haematopoietic stem cell transplantation (HSCT). The current standard of care for paediatrics in Australia involves pharmacogenomic testing for TPMT and NUD15, for patients with acute lymphoblastic leukaemia. Participants of the study will receive pharmacogenomic testing across a range of clinically relevant variants. Participants will be randomised to either the control arm or the study arm. Test results for participants in the study arm will be used to guide the dose and drug selection of 27 drugs commonly used in supportive care. The pharmacogenomic test results will be released to the study arm at week 4 and to the control arm at week 13, after the 12 week intervention period.

To determine whether pre-emptive pharmacogenomic testing does reduce clinically relevant adverse drug reactions, the Paediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) survey will be delivered at 3 time points within a 12 week period. This survey is a patient reported outcome measurement tool developed to evaluate symptomatic toxicity in participants receiving cancer therapy. After survey completion, semi-structured interviews will be conducted by an academic pharmacist with the aim of generating a CTCAE grade of severity for each of the symptoms defined in the Ped-PRO-CTCAE and assessing the causality of an adverse drug reaction using the Liverpool Adverse Drug Reaction Causality Assessment Tool (Liverpool ADR-CAT). These mechanisms will support the assessment of both severity and causality of any adverse drug reactions.

To evaluate the economic and Quality of Life impacts (QoL), participants will also complete The Child Health Utility 9D (CHU9D) QoL surveys specific to children and young adults at 3 timepoints over the 12-month period and consent to a Health Economics Analysis. This includes collection of Medicare Benefits Schedule (MBS)/ Pharmaceutical Benefits Scheme (PBS) data from Services Australia and Victorian Data Linkage Group to compare the costs of management of both the control and study arm.

Data from the study will be securely stored on the REDCap database. Patients will be allocated a unique patient identifier prior to their de-identified data being added to the database.

Eligibility criteria: Inclusion Criteria:

* Age \< 18 years
* New cancer diagnosis or patient receiving HSCT.
* Must receive a first prescription for one or more of the drugs for which the CPIC guideline is available, which is prescribed to them in routine care.
* Parent or patient is able and willing to give consent for patient to take part and be followed up for at least 12 weeks.
* Patient is amenable to venepuncture and blood draw (5mL \< 40 kgs, 12 mL \> 40kgs)
* Patient and/or parent is able and willing to sign an informed consent form.
* Patient and/or parent is able to complete Ped-PRO-CTCAE survey in English, Italian or Chinese.
* Study enrolment limit has not been reached.

Exclusion Criteria:

* Age \> 18 years.
* Patient has a life expectancy estimated to be less than three months by the treating clinical team.
* Duration of the drug of inclusion total treatment length is planned to be less than one week.
* Patient and/or parent is unable to consent to the study.
* Patient and/or parent is unwilling to take part in the study.
* Patient and/or parent is able unable to complete Ped-PRO-CTCAE survey in English, Italian or Chinese.
* Patient has existing impaired hepatic or renal function for which a lower dose or alternate drug selection are already part of current routine care.
* Patient has a glomerular filtration rate of less than 15 mL/min per 1.73m2.
* Patient has advanced liver failure.

Primary outcomes:
measure: Reduction in the number of adverse drug reactions (ADRs)
timeFrame: 12 weeks
Secondary outcomes:
measure: Occurrence of at least one ADR which contributes to primary endpoint
timeFrame: 12 weeks
measure: Occurrence of at least one causal, clinically relevant, drug-genotype specific ADR, attributable to the index drug.
timeFrame: 12 weeks
measure: Number of self-reported ADRs
timeFrame: 12 weeks
measure: Number of serious self-reported ADRs
timeFrame: 12 weeks
measure: Number of dose adjustments
timeFrame: 12 weeks
measure: Incidence of drug cessation due to ADR
timeFrame: 12 months
measure: Incidence of drug cessation due to lack of efficacy
timeFrame: 12 months
measure: Therapeutic drug monitoring
timeFrame: 12 months
measure: Physician and Pharmacist adherence to the CPIC guidelines
timeFrame: 12 months
measure: Health care expenditure related to adverse events using MBS/PBS data
timeFrame: 12 months
measure: Change in quality of life outcomes using CHU9D
timeFrame: Baseline, Week 12, 12 months
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Parkville
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
Study officials:
affiliation: The Royal Children's Hospital/Murdoch Children's Research Institute
name: A/Prof Rachel Conyers
role: PRINCIPAL_INVESTIGATOR
References: