The 5-FU Holter Study

University of Auckland, New Zealand

Status: Enrolling

Conditions: Gastrointestinal Malignancy

Treatments: Device: Holter monitor

Study type: Interventional

Funder types: Other

Identifiers

NCT06538610

CTNZ-2022-08

U1111-1308-6717 (Other Identifier)

Details and patient eligibility

About

To assess the feasibility of using ambulatory ECG monitoring (Holter monitor) for patients receiving 5-FU chemotherapy

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Holter monitor

Experimental group

Description:

Holter monitor for 48 hours

Treatment:

Device: Holter monitor