PhaRmacogEnomiC medIcines optimiSatIon for peOple with caNcer – a multicentre teletrial enabled Interrupted Time Series trial (PRECISION-ITS): A nested cohort substudy evaluating the safety & efficacy of 5-Fluorouracil Therapeutic Drug Monitoring in patients with metastatic/unresectable colorectal cancer.
Peter MacCallum Cancer Centre
200 participants
Aug 28, 2024
Interventional
Conditions
Summary
This multi-centre, prospective, tele-trial aims to evaluate the safety and efficacy of 5-Fluorouracil (5-FU) Therapeutic Drug Monitoring (TDM) in patients with metastatic/unresectable colorectal cancer. This trial will also assess the feasibility and acceptability of participants to conduct 'at-home' TDM self-testing. Who is it for? You may be eligible to join this study if you are aged 18 years and older, and are planning to commence infusional 5-FU-based chemotherapy that is used first-line or subsequent line (if being treated with irinotecan for the first time) for metastatic/unresectable colorectal cancer. Study details This is a sub-study of the PRECISION-ITS trial, all participants in this substudy will also participate in the primary PRECISION-ITS trial. In this substudy, patients will receive combined pharmacogenomics and TDM prescribing for 5-FU. Pharmacogenomic test results and dosing recommendations (based on panel results) will be provided to all participants and their clinician before commencement of chemotherapy. TDM test results and dosing recommendations will be reported by the pharmacogenomics pharmacist to the participant's clinician(s) in real-time before the next chemotherapy cycle. TDM will commence from the first cycle of chemotherapy and continue at consecutive chemotherapy cycles until target 5-FU drug levels are reached. At each chemotherapy cycle requiring TDM, participants will be asked to provide blood samples 3-17 hours and 18-40 hours after commencement of infusional 5-FU. The first sample will be self-collected by participants via finger prick blood collection devices, The second sample (consisting of finger prick and venous blood samples) will be collected by site staff. Participants will receive education from the pharmacogenomics pharmacist on how to conduct TDM self-testing and sample delivery. It is hoped that this trial will show that a combined pharmacogenomics/TDM prescribing approach for 5-FU increases treatment response to 5-FU based chemotherapy in metastatic/unresectable colorectal cancer, and that 'at-home', finger prick TDM testing by patients is feasible (thereby reducing patient burden for venous blood tests).
Eligibility
Plain Language Summary
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Interventions
The intervention is combined TDM and PGx-guided 5-FU prescribing. 5-FU TDM results, including recommended dose adjustments based on exposure levels (AUC), will be provided to the treating clinician based on the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5-Fluorouracil Therapy. It is the decision of the clinician to implement/not implement dose changes after considering both exposure levels and other clinical factors such as observed toxicities and treatment intent/patient goals of care. TDM will commence from the patient’s first chemotherapy cycle and will be repeated at consecutive chemotherapy cycles of 5-FU until the target AUC is reached (20-30mg – h/L). Dosing recommendations will be based on single timepoint blood sample collection 18-40hours after commencement of infusional 5-FU. At trial commencement this will be based on peripheral blood sample results, with the aim for within trial validation and conversion to finger prick blood sampling. The first set of samples (consisting of 2 finger prick blood samples) will be self-collected by participants 3-17 hours after commencement of infusional 5-FU. The second set of samples (consisting of 1 peripheral + 2 finger prick blood samples) will be collected by qualified site staff 18-40 hours after commencement of infusional 5-FU to ensure viable samples are consistently collected and to allow for feasibility assessments of patient self-testing. Patients will receive a TDM self-testing kit (designed specifically for this substudy) and education from the pharmacogenomics pharmacist on how to use the kit. Finger prick blood samples will be collected with a Volumetric Absorptive Microsampling (VAMS) device and dried plasma separation card. Participants recruited in this substudy will also participate in the PRECISION-ITS primary PGx trial and undergo PGx testing/prescribing/clinical follow up (as per the primary PGx trial), but will have additional trial visits due to TDM. Participants enrolled in Time Series 1 and 2 in the primary PGx trial will be able to participate in this substudy if they are receiving infusional 5-FU for metastatic/unresectable colorectal cancer. In the primary PGx trial, Time Series 2 will commence 3-4 months after accrual to Time Series 1 is completed.
Locations(8)
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ACTRN12624000078550