The 5-FU Holter Study

Официальное название

Feasibility Study of Ambulatory Holter Monitoring While Receiving Infusional Fluorouracil (5-FU) Chemotherapy

Обзор

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

Подробное описание

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.

Вмешательства

• Устройство Holter 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.

Первичные конечные точки

• Recruitment rate [Срок оценки: Up to 1 year]
• Acceptability rate [Срок оценки: Up to 1 year]
• Completion rate [Срок оценки: Up to 1 year]
• Overall time required to recruit to the target sample size [Срок оценки: Up to 1 year]
• Clinician experience of recruitment [Срок оценки: After 1 year]
• Clinician experience of barriers to recruitment [Срок оценки: After 1 year]
• Clinician experience of software module (Pathfinder SL) to measure ST segments using Holter monitoring while receiving infusional 5-FU chemotherapy [Срок оценки: After 1 year]
• FBAL (fluoro-beta-alanine) Excretion rate [Срок оценки: 3 hours]
• FBAL (fluoro-beta-alanine) Area under the Curve (AUC) [Срок оценки: 0, 20 minutes, 1 hour, 3 hours]
• FBAL (fluoro-beta-alanine) Clearance (CL) [Срок оценки: 0, 20 minutes, 1 hour, 3 hours]

Критерии участия

Критерии включения

• 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

Критерии исключения

• ECG with left bundle branch block or left ventricular hypertrophy with strain

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Новая Зеландия · 1 центр

• Auckland City Hospital — Auckland

Идентификаторы

NCT: NCT06538610 · CTNZ-2022-08 · U1111-1308-6717

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗