Gastrointestinal Malignancy
Conditions
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.
Interventions
DEVICEHolter monitor
Holter monitor fitted from start of 5-FU infusion (Day 1) to 5-FU infusion ending (Day 3). Holter monitor to be worn for approximately 46-48 hours.
Sponsors
Gut Cancer Foundation
Auckland City Hospital
The Heart Group
University of Auckland, New Zealand
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
• ECG with left bundle branch block or left ventricular hypertrophy with strain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment rate | Up to 1 year | The percentage of participants who were contacted and joined the study will be reported. |
| Acceptability rate | Up to 1 year | The percentage of participants who joined the study and wore the Holter monitor for the required study duration. |
| Completion rate | Up to 1 year | The percentage of participants who joined the study and completed all study assessments |
| 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. |
| 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 barriers to recruitment | After 1 year | Clinician Survey administered at end of study recruitment to measure clinicians' perceived barriers to recruitment (open ended questions) |
| 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) |
| 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 |
Countries
New Zealand
Contacts
Primary ContactJade Scott
Backup ContactSarah Benge
Outcome results
None listed