Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study (CardioSwitch)

December 7, 2024 updated by: Pia Osterlund, Helsinki University Central Hospital

Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity in Patients with Solid Tumors: a Retrospective, International and Non-interventional Study

The purpose of the present study is to evaluate cardiotoxicity during re-challenge of a different modality of fluoropyrimidine (primary end-point S-1 and secondary any other fluoropyrimidine) after having perceived cardiotoxicity with a fluoropyrimidine based regimen previously. The patient population is being treated for solid tumors.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Fluoropyrimidine chemotherapy agents, such as 5-fluorouracil and capecitabine, are occasionally associated with cardiotoxicity that may manifest as chest pain, ECG alterations, cardiac arrhythmia, and rarely myocardial infarction and sudden death. Clinical fluoropyrimidine cardiotoxicity is infrequent (1-8% of patients), but subclinical toxicity may be much more common (up to one third of patients). The underlying mechanisms are not well understood, but they may include abnormal coronary artery contractility or spasm, and myocardial toxicity. Cardiotoxicity may be less frequent with S-1 (a combination of tegafur, gimeracil and oteracil at a molar ratio of 1:0.4:1) as compared with 5-fluorouracil and capecitabine, but head-to-head comparisons are lacking.

Anecdotal evidence suggests that patients who have cardiotoxicity on other fluoropyrimidines may be successfully treated with S-1. The purpose of this retrospective study is to compare different 5-fluorouracil-based dosing modalities and S-1, and compare cardiotoxicity during these treatments.

The patient population was treated for solid tumors with a 5-fluorouracil based regimen and had a cardiac event grade 1-4. All patients were re-challenged with a different fluoropyrimidine or S-1 and assessed for cardiotoxicity during re-challenge.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Odense, Denmark
        • Odense University Hospital
  • Finland
      • Oulu, Finland
        • Oulu University Hospital
      • Turku, Finland
        • Turku University Hospital
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Department of Oncology
    • Uusimaa
      • Helsinki, Uusimaa, Finland, 00290
        • Helsinki University Central Hospital
  • Iceland
      • Reykjavík, Iceland
        • Landspitali
  • Ireland
      • Dublin, Ireland
        • St. Vincents University Hospital
  • Netherlands
      • Amsterdam, Netherlands
        • Academic Medical Center
  • Norway
      • Bergen, Norway
        • Haukeland University Hospital
  • Sweden
      • Lund, Sweden
        • Skone university hospital
      • Stockholm, Sweden
        • Karolinska University Hospital
      • Sundsvall, Sweden
        • Sundsvall Hospital
      • Uppsala, Sweden
        • Uppsala Academic Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All consecutive patients who fulfil the following inclusion criteria will be included in the database until the target number of patients has been included:

  • Solid tumor
  • Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment
  • Re-challenge with a different fluoropyrimidine-based treatment. Primary endpoint is switch to S-1 and secondary any fluoropyrimidine population.

Description

Inclusion Criteria:

  • Solid tumor
  • Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment
  • Re-challenge with a different fluoropyrimidine-based therapy

Exclusion Criteria:

• Participation in a trial with experimental drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment
Time Frame: After switch to and during one line of S-1 based chemotherapy (average 6 months)
Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to S-1
After switch to and during one line of S-1 based chemotherapy (average 6 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine
Time Frame: After switch to and during one line of another fluoropyrimidine regimen (average 6 months)
Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to another fluoropyrimidine chemotherapy
After switch to and during one line of another fluoropyrimidine regimen (average 6 months)
Cardiac symptoms during fluoropyrimidine chemotherapy
Time Frame: During one line of fluoropyrimidine based chemotherapy (average 6 months)
Frequency and severity according to NCI-CTCAE of cardiac symptoms during different fluoropyrimidines and the correlation with other added cytotoxics or biologics
During one line of fluoropyrimidine based chemotherapy (average 6 months)
Diagnostic work-up
Time Frame: During one line of fluoropyrimidine based chemotherapy (average 6 months)
Diagnostic work-up for cardiotoxicity in real world data
During one line of fluoropyrimidine based chemotherapy (average 6 months)
Time-lines for cardiotoxicity
Time Frame: During one line of fluoropyrimidine based chemotherapy (average 6 months)
Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy
During one line of fluoropyrimidine based chemotherapy (average 6 months)
Dose-intensity
Time Frame: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity
Dose-intensity of the therapy at the cycle causing cardiotoxicity
During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity
Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity
Time Frame: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity

The alterations of (if evaluated), graded as normal, non-significant abnormalities or significant abnormalities.:

  • ECG abnormalities
  • Ejection fraction in %
  • Coronary artery status on angiogram
  • Cardiac arrhythmias in ECG, Holter or cardiac monitor registration
  • Plasma troponin concentration and other cardiac enzymes and other laboratory tests as within reference range ro abnormal
  • Serum alpha-fluoro-beta-alanine (FBAL) concentration
During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Helsinki University Central Hospital

Collaborators

Tampere University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2018

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

January 22, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (Actual)

February 7, 2020

Study Record Updates

Last Update Posted (Estimated)

December 12, 2024

Last Update Submitted That Met QC Criteria

December 7, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R18045

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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