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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05667766




Registration number
NCT05667766
Ethics application status
Date submitted
19/12/2022
Date registered
29/12/2022
Date last updated
21/06/2024

Titles & IDs
Public title
Minimising Adverse Drug Reactions and Verifying Economic Legitimacy in Children (MARVEL-PIC)
Scientific title
Minimising Adverse Drug Reactions and Verifying Economic Legitimacy - Pharmacogenomics Implementation in Children (MARVEL-PIC)
Secondary ID [1] 0 0
89083
Universal Trial Number (UTN)
Trial acronym
MARVEL-PIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Bone Marrow Transplantation 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - Release of Extended Pharmacogenomics Report at Week 1
Diagnosis / Prognosis - Release of Extended Pharmacogenomics Report at Week 13

Other: Standard of Care - Standard of Care prescribing for period of 12 months. Participants will receive pharmacogenomic test results according to the current standard of care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.

Experimental: Experimental Arm - Extended Pharmacogenomic prescribing for a period of 12 months. Participants will receive pharmacogenomic testing across a range of clinically relevant variants, to guide the dose and drug selection of 27 drugs commonly used in supportive care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.


Diagnosis / Prognosis: Release of Extended Pharmacogenomics Report at Week 1
Whole genome sequencing with reporting on current standard of care (SoC) pharmacogenomic variants (TPMT, NUD15) where applicable (i.e, for patients with diagnosis of acute lymphoblastic leukaemia) by Week 1. Whole genome sequencing on a broader number of actionable variants as per international guidelines for cancer supportive care (identical to study arm) will be reported on at Week 13.

Diagnosis / Prognosis: Release of Extended Pharmacogenomics Report at Week 13
Whole genome sequencing with reporting on current standard of care (SoC) pharmacogenomic variants (TPMT, NUD15) where applicable (i.e, for patients with diagnosis of acute lymphoblastic leukaemia) and reporting of a broader number of actionable pharmacogenomic variants as per international guidelines for cancer supportive care reported on by Week 1.
Intervention code [1] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Reduction in the number of adverse drug reactions (ADRs)
Assessment method [1] 0 0
The primary outcome is a reduction in adverse drug reactions among patients with actionable pharmacogenomic variants. An adverse drug reaction will be considered as any CTCAE grade 2 and above for non-haematological toxicities or CTCAE grade 3 and above for haematological toxicities. CTCAE grades are defined as 1,2,3,4 or 5, with 5 indicating the most severe.
Timepoint [1] 0 0
12 weeks
Secondary outcome [1] 0 0
Occurrence of at least one ADR which contributes to primary endpoint
Assessment method [1] 0 0
An adverse drug reaction will be considered as any CTCAE grade 2 and above for non-haematological toxicities or CTCAE grade 3 and above for haematological toxicities. This includes an ADR which was caused either by the index drug of inclusion or any subsequent drug. CTCAE grades are defined as 1,2,3,4 or 5, with 5 indicated the most severe.
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Occurrence of at least one causal, clinically relevant, drug-genotype specific ADR, attributable to the index drug.
Assessment method [2] 0 0
The Liverpool ADR CAT is an assessment tool produced to attribute causality to specific drugs for the grading of ADR symptomatic toxicity. Possible grading of ADRs include either definite, probable or possible.
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Number of self-reported ADRs
Assessment method [3] 0 0
The Ped-PRO-CTCAE survey is an electronic patient reported outcome measurement survey developed to evaluate symptomatic toxicity in patients who are receiving cancer therapy. Symptoms are evaluated for attributes of frequency, severity, interference, amount, presence or absence. Each symptomatic adverse event (AE) is assessed by 1-3 attributes that can be linked back to a CTCAE grade. The number of self-reported ADRs are measured independent of severity or drug-gene association but caused by one of the chemotherapeutic /targeted agents.
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Number of serious self-reported ADRs
Assessment method [4] 0 0
The Ped-PRO-CTCAE survey is an electronic patient reported outcome measurement survey developed to evaluate symptomatic toxicity in patients who are receiving cancer therapy. Symptoms are evaluated for attributes of frequency, severity, interference, amount, presence or absence. Each symptomatic adverse event (AE) is assessed by 1-3 attributes that can be linked back to a CTCAE grade. The number of self-reported ADRs are measured independent of severity or drug-gene association but caused by one of the chemotherapeutic /targeted agents. An ADR will be classified as serious if that event led to death, serious deterioration in health, or fetal distress.
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Number of dose adjustments
Assessment method [5] 0 0
Number of dose adjustments made to drug-gene associated therapy during the entire study follow up by review of the participants electronic medical record and medication reconciliation.
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
Incidence of drug cessation due to ADR
Assessment method [6] 0 0
Incidence of drug cessation due to ADR during the entire study follow up. Relates to inclusion criteria drug by review of the participants electronic medical record and medication reconciliation.
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Incidence of drug cessation due to lack of efficacy
Assessment method [7] 0 0
Incidence of drug cessation due to lack of efficacy by review of the participants electronic medical record and medication reconciliation.
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Therapeutic drug monitoring
Assessment method [8] 0 0
Therapeutic drug monitoring (routine drug levels) performed during entire study follow up period by review of the participants electronic medical record and medication reconciliation.
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Physician and Pharmacist adherence to the CPIC guidelines
Assessment method [9] 0 0
After discussion and consensus of a pharmacogenetic variant. A clinical report will be generated with the results and therapeutic recommendations according to Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Adherence to recommendations will be reported with reasoning, during the 12 week period.
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Health care expenditure related to adverse events using MBS/PBS data
Assessment method [10] 0 0
Data will be collected on the costs of management comparing the standard of care arm versus the study arm. The actual costs assigned to each inpatient or outpatient episode will be collected. This information is readily accessible through Services Australia and The Department of Health via The Centre for Victorian Data Linkage (CVDL).
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
Change in quality of life outcomes using CHU9D
Assessment method [11] 0 0
The University of Sheffield CHU9D Quality of Life Survey will be used to monitor changes in patient QoL. The CHU9D consists of a descriptive system and set of preference weights, for 9 questions that assess participants daily functioning across the following domains: worry, sadness, pain, tiredness, annoyance, school, sleep, daily routine and activities. The tool allows for calculation of quality adjusted life years for use in cost utility analysis
Timepoint [11] 0 0
Baseline, Week 12, 12 months

Eligibility
Key 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.
Minimum age
No limit
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
880
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [3] 0 0
The Royal Children's Hospital - Parkville
Recruitment hospital [4] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5006 - North Adelaide
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
A/Prof Rachel Conyers
Address 0 0
The Royal Children's Hospital/Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tayla Stenta
Address 0 0
Country 0 0
Phone 0 0
03 9345 5533
Email 0 0
pharmaco.genomics@mcri.edu.au
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05667766