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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06383338




Registration number
NCT06383338
Ethics application status
Date submitted
21/03/2024
Date registered
25/04/2024
Date last updated
22/05/2024

Titles & IDs
Public title
A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma.
Scientific title
A Prospective Feasibility Study Investigating PhEnoconversion of CYP3A4, CYP2C19 and CYP2D6 Genotype in Paediatric and Adolescent and Young Adult patientS With an acUte diagnosiS of Hodgkin or Non-Hodgkin Lymphoma.
Secondary ID [1] 0 0
PEGASUS
Universal Trial Number (UTN)
Trial acronym
PEGASUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 0 0
Non Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Omeprazole
Treatment: Drugs - Dextromethorphan

Treatment: Drugs: Omeprazole
Sub-therapeutic probe drug administration to measure phenoconversion.

Treatment: Drugs: Dextromethorphan
Sub-therapeutic probe drug administration to measure phenoconversion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
12 months, 24 Months
Secondary outcome [1] 0 0
Percentage of participants completing all required longitudinal blood sampling
Timepoint [1] 0 0
Baseline through to 24 Months
Secondary outcome [2] 0 0
Proportion of participants with successful detection of probe drug overall and at each sampling timepoint
Timepoint [2] 0 0
Baseline through to 24 Months
Secondary outcome [3] 0 0
Proportion of participants where phenotype can be classified according to MR overall at each sampling timepoint
Timepoint [3] 0 0
Baseline through to 24 Months
Secondary outcome [4] 0 0
The level of acceptability of participation in pharmacogenomic & phenoconversion testing using the PEGASUS specific survey tool (based on the Theoretical Framework of Acceptability [TFA])
Timepoint [4] 0 0
Baseline through to 24 Months
Secondary outcome [5] 0 0
Percentage of participants experiencing an adverse event (AE) during probe drug administration
Timepoint [5] 0 0
Baseline through to 24 Months
Secondary outcome [6] 0 0
Incidence of genotype and phenotype mismatch, overall and across longitudinal timepoints
Timepoint [6] 0 0
Baseline through to 24 Months
Secondary outcome [7] 0 0
Proportion of participants with disease staging and biomarkers of extent of disease
Timepoint [7] 0 0
Baseline through to 24 Months
Secondary outcome [8] 0 0
Proportion of participants with a systemic inflammatory state
Timepoint [8] 0 0
Baseline through to 24 Months
Secondary outcome [9] 0 0
Proportion of participants taking medications involving the CYP P450 pathway
Timepoint [9] 0 0
Baseline through to 24 Months
Secondary outcome [10] 0 0
Participant demographic information
Timepoint [10] 0 0
Baseline
Secondary outcome [11] 0 0
Proportion of participants with other environmental factors
Timepoint [11] 0 0
Baseline through to 24 Months
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline through to 24 Months

Eligibility
Key inclusion criteria
- 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.
Minimum age
6 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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).

- Is a clinically unstable patient requiring intensive care admission in high-risk
circumstances will not be considered eligible for consent.

- Any patient requiring urgent initiation of anti-cancer treatment outside hours where a
member of the study staff is unable to approach the parent/guardian or participant for
consent prior to commencing anti-cancer therapy will be ineligible for consent.

- Unable to provide written informed consent.

Study design
Purpose of the study
Basic Science
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2026
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

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

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06383338
Trial related presentations / publications
Helsby N, Yong M, Burns K, Findlay M, Porter D. Cyclophosphamide bioactivation pharmacogenetics in breast cancer patients. Cancer Chemother Pharmacol. 2021 Sep;88(3):533-542. doi: 10.1007/s00280-021-04307-0. Epub 2021 Jun 10.
Burns KE, Goldthorpe MA, Porteus F, Browett P, Helsby NA. CYP2C19 genotype-phenotype discordance in patients with multiple myeloma leads to an acquired loss of drug-metabolising activity. Cancer Chemother Pharmacol. 2014 Mar;73(3):651-5. doi: 10.1007/s00280-014-2409-9. Epub 2014 Feb 12.
Kim S, Ostor AJ, Nisar MK. Interleukin-6 and cytochrome-P450, reason for concern? Rheumatol Int. 2012 Sep;32(9):2601-4. doi: 10.1007/s00296-012-2423-3. Epub 2012 Mar 27.
Rodieux F, Daali Y, Rollason V, Samer CF, Ing Lorenzini K. Practice of CYP450 genotyping and phenotyping in children in a real-life setting. Front Pharmacol. 2023 Feb 27;14:1130100. doi: 10.3389/fphar.2023.1130100. eCollection 2023.
Bosilkovska M, Samer CF, Deglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.
Lloret-Linares C, Rollason V, Lorenzini KI, Samer C, Daali Y, Gex-Fabry M, Aubry JM, Desmeules J, Besson M. Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study. Pharmacol Res. 2017 Apr;118:104-110. doi: 10.1016/j.phrs.2016.07.002. Epub 2016 Jul 1.
Rollason V, Lloret-Linares C, Lorenzini KI, Daali Y, Gex-Fabry M, Piguet V, Besson M, Samer C, Desmeules J. Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study. J Pers Med. 2020 Oct 27;10(4):198. doi: 10.3390/jpm10040198.
Ing Lorenzini K, Desmeules J, Rollason V, Bertin S, Besson M, Daali Y, Samer CF. CYP450 Genotype-Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting. Front Pharmacol. 2021 Aug 26;12:730637. doi: 10.3389/fphar.2021.730637. eCollection 2021.
Lenoir C, Niederer A, Rollason V, Desmeules JA, Daali Y, Samer CF. Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics. CPT Pharmacometrics Syst Pharmacol. 2022 Jan;11(1):30-43. doi: 10.1002/psp4.12730. Epub 2021 Nov 17.
Mandrioli R, Mercolini L, Protti M. Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption. Molecules. 2020 Feb 26;25(5):1046. doi: 10.3390/molecules25051046.
Doerflinger M, Haeusler GM, Li-Wai-Suen CSN, Clark JE, Slavin M, Babl FE, Allaway Z, Mechinaud F, Smyth GK, De Abreu Lourenco R, Phillips B, Pellegrini M, Thursky KA. Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia. Front Immunol. 2021 May 20;12:641879. doi: 10.3389/fimmu.2021.641879. eCollection 2021.
Public notes

Contacts
Principal investigator
Name 0 0
Rachel Conyers, MBBS (Hons)
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Rachel Conyers, MBBS (Hons)
Address 0 0
Country 0 0
Phone 0 0
+61393455522
Fax 0 0
Email 0 0
rachel.conyers@mcri.edu.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06383338