CardioSwitch: Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study

Sponsor

Helsinki University Central Hospital (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04260269

Collaborator

Tampere University Hospital (Other)

200

Enrollment

Locations

Anticipated Duration (Months)

15.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: Fluoropyrimidine

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 Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2025

Outcome Measures

Primary Outcome Measures

Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment [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

Secondary Outcome Measures

Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine [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
Cardiac symptoms during fluoropyrimidine chemotherapy [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
Diagnostic work-up [During one line of fluoropyrimidine based chemotherapy (average 6 months)]
Diagnostic work-up for cardiotoxicity in real world data
Time-lines for cardiotoxicity [During one line of fluoropyrimidine based chemotherapy (average 6 months)]
Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy
Dose-intensity [During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity]
Dose-intensity of the therapy at the cycle causing cardiotoxicity
Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Odense University Hospital	Odense		Denmark
2	Department of Oncology	Tampere	Pirkanmaa	Finland	33520
3	Helsinki University Central Hospital	Helsinki	Uusimaa	Finland	00290
4	Oulu university hospital	Oulu		Finland
5	Turku university hospital	Turku		Finland
6	Landspitali	Reykjavík		Iceland
7	St. Vincents University Hospital	Dublin		Ireland
8	Academic Medical Center	Amsterdam		Netherlands
9	Haukeland University Hospital	Bergen		Norway
10	Skone university hospital	Lund		Sweden
11	Karolinska University Hospital	Stockholm		Sweden
12	Sundsvall hospital	Sundsvall		Sweden
13	Uppsala academic hospital	Uppsala		Sweden