The 5-FU Holter Study

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

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

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Malignancy
• Intervention / Treatment: Device: Holter monitor

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Benge; Phone Number: +64276045647; Email: s.benge@auckland.ac.nz
• Study Contact Backup: Name: Jade Scott; Phone Number: +64 (0)9 923 4222; Email: j.scott@auckland.ac.nz

Study Locations

• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
    • Contact: Study Coordinator; Phone Number: 643074949; Email: researchassistant@adhb.govt.nz
    • Contact: Jane So

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Holter monitor; Holter monitor for 48 hours	Device: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	The percentage of participants who were contacted and joined the study will be reported.	Up to 1 year
Acceptability rate	The percentage of participants who joined the study and wore the Holter monitor for the required study duration.	Up to 1 year
Completion rate	The percentage of participants who joined the study and completed all study assessments	Up to 1 year
Overall time required to recruit to the target sample size	The overall time in weeks required to recruit participants for the feasibility study will be reported.	Up to 1 year
Clinician experience of recruitment	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)	After 1 year
Clinician experience of barriers to recruitment	Clinician Survey administered at end of study recruitment to measure clinicians' perceived barriers to recruitment (open ended questions)	After 1 year
Clinician experience of software module (Pathfinder SL) to measure ST segments using Holter monitoring while receiving infusional 5-FU chemotherapy	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)	After 1 year
FBAL (fluoro-beta-alanine) Excretion rate	Cumulative urine sample collected over 3 hours	3 hours
FBAL (fluoro-beta-alanine) Area under the Curve (AUC)	Blood samples collected prechemo and 20 mins, 1 hour, 3 hours	0, 20 minutes, 1 hour, 3 hours
FBAL (fluoro-beta-alanine) Clearance (CL)	Blood samples collected prechemo and 20 mins, 1 hour, 3 hours	0, 20 minutes, 1 hour, 3 hours

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Collaborators: Auckland City Hospital; Gut Cancer Foundation; The Heart Group

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: August 4, 2024
• First Posted (Actual): August 6, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CTNZ-2022-08; U1111-1308-6717 (Other Identifier: The Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No