The 5-FU Holter Study

Trial Title: The 5-FU Holter Study

NCT ID: NCT06538610

Condition: Gastrointestinal Malignancy

Conditions: Official terms:
Neoplasms

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Diagnostic

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Holter monitor
Description: 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.
Arm group label: Holter monitor

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.

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: October 2024

Completion date: January 2026

Lead sponsor:
Agency: University of Auckland, New Zealand
Agency class: Other

Collaborator:
Agency: Gut Cancer Foundation
Agency class: Other

Collaborator:
Agency: Auckland City Hospital
Agency class: Other

Collaborator:
Agency: The Heart Group
Agency class: Other

Source: University of Auckland, New Zealand

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06538610