PEGASUS aims to test acceptability and feasibility of studying phenoconversion (the change in metabolism phenotype) using probe medications in a paediatric oncology patient population. The study will be conducted in patients (6-25 years of age) with Hodgkin lymphoma or non-Hodgkin lymphoma as exemplar cohort, but with the understanding that cancer-directed and supportive care medicines of the CYP3A4, CYP2C19, and CYP2D6 metabolic pathways are commonly utilised for the treatment of many paediatric, adolescent, young adult, and adult cancers. The study involves administration of the probe medication at timepoints which align with pre-determined hospital visits for the treatment of lymphoma and subsequent blood draws to measure the metabolism of the probe medications. The acceptability and feasibility of this study will inform future studies in phenoconversion within the paediatric cancer population to direct more personalised precision medicine.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
10
Sub-therapeutic probe drug administration to measure phenoconversion.
Sub-therapeutic probe drug administration to measure phenoconversion.
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGProportion of patients who consent to study and complete baseline and at least two longitudinal timepoints with successful measurement of probe drug MR (Metabolic ratio)
This measure is to help inform whether future studies of this nature are feasible and identify if any procedures need to be adjusted to ensure study participant completion.
Time frame: 12 months, 24 Months
Percentage of participants completing all required longitudinal blood sampling
This measure is to help inform whether future studies of this nature are feasible and identify if any procedures need to be adjusted to ensure study participant completion.
Time frame: Baseline through to 24 Months
Proportion of participants with successful detection of probe drug overall and at each sampling timepoint
This measure is to help inform whether future studies of this nature are feasible and identify if the method for probe drug detection requires improvement.
Time frame: Baseline through to 24 Months
Proportion of participants where phenotype can be classified according to MR overall at each sampling timepoint
This measure is to help inform whether future studies of this nature are feasible and identify if the phenotype can be clearly classified at each timepoint; (i) Prior to commencing first lymphoma chemotherapy cycle (ii) 2 months (week 8) (iii) 4 months (week 16) (iv) Completion of therapy (\> week 16) (v) Up to a maximum of 2 febrile neutropenic episodes and for how many patients.
Time frame: Baseline through to 24 Months
The level of acceptability of participation in pharmacogenomic & phenoconversion testing using the PEGASUS specific survey tool (based on the Theoretical Framework of Acceptability [TFA])
This measure is to help inform whether future studies of this nature are feasible and acceptable. Participants will complete the survey which asks 26 questions, with a numerical scale of 1-7 or a wording scale of 7 choices depending on the question.
Time frame: Baseline through to 24 Months
Percentage of participants experiencing an adverse event (AE) during probe drug administration
This measure is to help inform whether future studies of this nature are feasible and identify if/how many adverse events are experienced during probe drug administration.
Time frame: Baseline through to 24 Months
Incidence of genotype and phenotype mismatch, overall and across longitudinal timepoints
This measure is to help inform whether future studies of this nature are feasible and identify if genotype and phenotype mismatch occurs throughout each timepoint and the overall study.
Time frame: Baseline through to 24 Months
Proportion of participants with disease staging and biomarkers of extent of disease
This measure is to help inform whether future studies of this nature are feasible, to identify any variables that stand out and inform future research questions.
Time frame: Baseline through to 24 Months
Proportion of participants with a systemic inflammatory state
This measure is to help inform whether future studies of this nature are feasible, to identify any variables that stand out and inform future research questions.
Time frame: Baseline through to 24 Months
Proportion of participants taking medications involving the CYP P450 pathway
This measure is to help inform whether future studies of this nature are feasible, to identify any variables that stand out and inform future research questions.
Time frame: Baseline through to 24 Months
Participant demographic information
This measure is to help inform whether future studies of this nature are feasible, to identify any variables that stand out and inform future research questions.
Time frame: Baseline
Proportion of participants with other environmental factors
This measure is to help inform whether future studies of this nature are feasible, to identify any variables that stand out and inform future research questions.
Time frame: Baseline through to 24 Months
Longitudinal inflammatory profile of participants with Hodgkin or non-Hodgkin Lymphoma as measured by a panel including serum levels of procalcitonin, c-reactive protein and cytokine analysis.
This measure is to identify if there are fluctuations within the inflammatory profile of the patients which helps to inform whether future studies of this nature are feasible. The panel detects a comprehensive set of studied and biologically relevant inflammatory markers including those shown to be predictive of severe infection in children with cancer and febrile neutropenia when out of normal ranges.
Time frame: Baseline through to 24 Months
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