Clinical trial NCT06538610: The 5-FU Holter Study
Official title: Feasibility Study of Ambulatory Holter Monitoring While Receiving Infusional Fluorouracil (5-FU) Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gastrointestinal Malignancy
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
Collaborators: name: Gut Cancer Foundation
name: Auckland City Hospital
name: The Heart Group
First posted: 2024-08-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment rate
timeFrame: Up to 1 year
measure: Acceptability rate
timeFrame: Up to 1 year
measure: Completion rate
timeFrame: Up to 1 year
measure: Overall time required to recruit to the target sample size
timeFrame: Up to 1 year
measure: Clinician experience of recruitment
timeFrame: After 1 year
measure: Clinician experience of barriers to recruitment
timeFrame: After 1 year
measure: Clinician experience of software module (Pathfinder SL) to measure ST segments using Holter monitoring while receiving infusional 5-FU chemotherapy
timeFrame: After 1 year
measure: FBAL (fluoro-beta-alanine) Excretion rate
timeFrame: 3 hours
measure: FBAL (fluoro-beta-alanine) Area under the Curve (AUC)
timeFrame: 0, 20 minutes, 1 hour, 3 hours
measure: FBAL (fluoro-beta-alanine) Clearance (CL)
timeFrame: 0, 20 minutes, 1 hour, 3 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
References: