The 5-FU Holter Study
- Conditions
- Gastrointestinal Malignancy
- Interventions
- Device: Holter monitor
- Registration Number
- NCT06538610
- Lead Sponsor
- University of Auckland, New Zealand
- Brief Summary
To assess the feasibility of using ambulatory ECG monitoring (Holter monitor) for patients receiving 5-FU chemotherapy
- Detailed Description
5-fluorouracil (5-FU) is the key chemotherapy component in systemic treatment of colorectal cancer. However, 5-FU treatment is also associated with cardiotoxicity which can have devastating consequences.
Cardiotoxicity can be both symptomatic (e.g. chest pain, myocardial infarction (heart attack) and/or sudden death) as well as asymptomatic ('silent myocardial ischemia', which is only detectable by ECG). Data suggests that asymptomatic cardiotoxicity may be relatively common (\~30% of patients).
About 69% of the cardiac events are seen during or within the first 72 hours of the first cycle of 5-FU.
The development of cardiotoxicity requires permanent discontinuation of 5-FU chemotherapy. There are no PHARMAC funded alternatives for patients who discontinue 5-FU due to cardiotoxicity. Discontinuation of 5-FU is likely to lead to a worse oncological outcome (survival time) for the patient.
One proposed mechanism for 5-FU cardiotoxicity involves fluoro-beta-alanine (FBAL), which is a metabolite formed when 5-FU is catalysed by the enzyme dihydropyrimidine dehydrogenase (DPD). The rationale for this feasibility study is to provide preliminary information required to develop a prospective pharmacokinetic study exploring plasma clearance of FBAL and 5-FU cardiotoxicity.
This study aims to determine i) whether the use of continuous ECG monitoring (ambulatory Holter monitoring) in real life conditions (over two days, while at home receiving infusional 5-FU chemotherapy), is able to appropriately assess these types of silent heart attacks (ST changes) and ii) the acceptability of this study to both patients and clinicians iii) the excretion rate of FBAL over the 48 hour time period \& interpatient pharmacokinetic variability in FBAL excretion.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
- Patients with diagnosis of gastrointestinal malignancy
- Planned to receive either FOLFOX chemotherapy with any treatment intent
- Aged ≥ 18 years at time of signing informed consent form
• ECG with left bundle branch block or left ventricular hypertrophy with strain
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Holter monitor Holter monitor Holter monitor for 48 hours
- Primary Outcome Measures
Name Time Method Recruitment rate Up to 1 year The percentage of participants who were contacted and joined the study will be reported.
Clinician experience of recruitment After 1 year Clinician Survey administered at end of study recruitment to measure clinicians' perceived ease of recruitment (5-point Likert scale 1=Difficult to 5=Very easy)
Clinician experience of software module (Pathfinder SL) to measure ST segments using Holter monitoring while receiving infusional 5-FU chemotherapy After 1 year Clinician Survey administered at the end of study recruitment to measure clinicians' perceived quality of Holter monitor recordings (5-point Likert scale 1=Poor to 5=Excellent)
Completion rate Up to 1 year The percentage of participants who joined the study and completed all study assessments
Acceptability rate Up to 1 year The percentage of participants who joined the study and wore the Holter monitor for the required study duration.
Clinician experience of barriers to recruitment After 1 year Clinician Survey administered at end of study recruitment to measure clinicians' perceived barriers to recruitment (open ended questions)
Overall time required to recruit to the target sample size Up to 1 year The overall time in weeks required to recruit participants for the feasibility study will be reported.
FBAL (fluoro-beta-alanine) Excretion rate 3 hours Cumulative urine sample collected over 3 hours
FBAL (fluoro-beta-alanine) Area under the Curve (AUC) 0, 20 minutes, 1 hour, 3 hours Blood samples collected prechemo and 20 mins, 1 hour, 3 hours
FBAL (fluoro-beta-alanine) Clearance (CL) 0, 20 minutes, 1 hour, 3 hours Blood samples collected prechemo and 20 mins, 1 hour, 3 hours
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Auckland City Hospital
🇳🇿Auckland, New Zealand