Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study

Solid Tumor Clinical Trial

— CardioSwitch  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04260269
• Other study ID #: R18045
• Status: Enrolling by invitation
• Start date: June 1, 2018
• Est. completion date: December 2025

Study information

• Verified date: February 2020
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiotoxicity
• Solid Tumor

Intervention

Drug:
• Fluoropyrimidine
This is the assessment of a specific evaluation of cardiac safety for patients with solid tumors who have experienced cardiotoxicity grade 1-4 during treatment with a fluoropyrimidine based treatment and are re-challenged with a different fluoropyrimidine. This multicentre, retrospective database is built to assess the impact on the cardiac and global safety of two different fluoropyrimidine based treatment regimens, of which the first has caused cardiotoxicity grade 1-4. Cardiac data will be collected by medical record review from initiation of first fluoropyrimidine-based treatment and switch to second fluoropyrimidine-based treatment until death or last follow-up. Basic demographics, cancer and treatment information from the whole course of cancer until death or last follow-up.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Tampere University Hospital

Countries where clinical trial is conducted

Denmark,  Finland,  Iceland,  Ireland,  Netherlands,  Norway,  Sweden, 

References & Publications (7)

Deboever G, Hiltrop N, Cool M, Lambrecht G. Alternative treatment options in colorectal cancer patients with 5-fluorouracil- or capecitabine-induced cardiotoxicity. Clin Colorectal Cancer. 2013 Mar;12(1):8-14. doi: 10.1016/j.clcc.2012.09.003. Epub 2012 Oct 26. Review. — View Citation

Kwakman JJ, Simkens LH, Mol L, Kok WE, Koopman M, Punt CJ. Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: A retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group. Eur J Cancer. 2017 May;76:93-99. doi: 10.1016/j.ejca.2017.02.009. Epub 2017 Mar 10. — View Citation

Kwakman JJM, Baars A, van Zweeden AA, de Mol P, Koopman M, Kok WEM, Punt CJA. Case series of patients treated with the oral fluoropyrimidine S-1 after capecitabine-induced coronary artery vasospasm. Eur J Cancer. 2017 Aug;81:130-134. doi: 10.1016/j.ejca.2017.05.022. Epub 2017 Jun 15. — View Citation

Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev. 2013 Dec;39(8):974-84. doi: 10.1016/j.ctrv.2013.03.005. Epub 2013 Apr 10. Review. — View Citation

Winther SB, Zubcevic K, Qvortrup C, Vestermark LW, Jensen HA, Krogh M, Sorbye H, Pfeiffer P; Academy of Geriatric Cancer Research (AgeCare). Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC): Findings from an observational chart review. Acta Oncol. 2016 Jul;55(7):881-5. doi: 10.3109/0284186X.2016.1161825. Epub 2016 May 16. — View Citation

Ye JX, Liu AQ, Ge LY, Zhou SZ, Liang ZG. Effectiveness and safety profile of S-1-based chemotherapy compared with capecitabine-based chemotherapy for advanced gastric and colorectal cancer: A meta-analysis. Exp Ther Med. 2014 May;7(5):1271-1278. Epub 2014 Feb 24. — View Citation

Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009 Jun 16;53(24):2231-47. doi: 10.1016/j.jacc.2009.02.050. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment	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	Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine	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)
Secondary	Cardiac symptoms during fluoropyrimidine chemotherapy	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)
Secondary	Diagnostic work-up	Diagnostic work-up for cardiotoxicity in real world data	During one line of fluoropyrimidine based chemotherapy (average 6 months)
Secondary	Time-lines for cardiotoxicity	Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy	During one line of fluoropyrimidine based chemotherapy (average 6 months)
Secondary	Dose-intensity	Dose-intensity of the therapy at the cycle causing cardiotoxicity	During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity
Secondary	Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity	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