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.
Age 6-25 years of age.
New diagnosis of Hodgkin Lymphoma or Non-Hodgkin Lymphoma.
Able to swallow and absorb oral or nasogastric tube (NGT) administration of probe drugs.
Able to provide written informed consent.
Failure to comply with inclusion criteria.
Has a known previous allergy to any of the probe medications (i.e., omeprazole or dextromethorphan).
Common Terminology Criteria for Adverse Events (CTCAE) Grade IV end organ dysfunction (i.e., hepatic, renal, gastrointestinal).
Had previous oncological treatment (not first cancer diagnosis).
Single group
Omeprazole
DrugSub-therapeutic probe drug administration to measure phenoconversion.
Dextromethorphan
DrugSub-therapeutic probe drug administration to measure phenoconversion.
Proportion 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.
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.
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.
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.
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.
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