None listed
Conditions
Brief 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).
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 tox
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.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: 1. Aged 18 years or older 2. Metastatic or unresectable colorectal cancer commencing first-line 5-FU based systemic anticancer therapy or 5-FU based systemic anticancer therapy with first exposure to irinotecan (utilised first or subsequent line); prior treatment for early stage disease permitted. 3. Diagnostic work-up and treatment planned to be undertaken at participating trial site. 4. Patient has capacity to provide consent using the ethics approved PICF, and has provided written informed consent. 5. Patient and/or carer can complete patient surveys 6. Study enrolment limit has not been reached
Exclusion criteria
Exclusion Criteria: 1. Commenced systemic anticancer therapy. 2. Referral to participating trial site for second opinion only, with no intent for treatment at the participating site. 3. Patients receiving a pharmacogenomics drug of interest (Appendix 1) as an investigational medicinal product in another interventional clinical drug trial that prohibits concurrent enrolment (as part of eligibility or PI’s discretion), or that represents an unreasonable burden of patient participation at the discretion of the patient or investigator. 4. Diagnosis of neuroendocrine cancer (due to differences in treatment pathways and routine follow-up schedules). 5. Patient is receiving HIPEC (due to differences in treatment pathways and routine follow-up schedules). 6. Does not meet inclusion criteria
Outcome results
None listed