AzTrials
AzTrials

Solid TumorCardioSwitchNCT04260269

Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study

An observational study of Solid Tumor, run by Helsinki University Central Hospital at 13 sites in 7 countries.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Fluoropyrimidine
How many people
200 participants
Where
13 sitesin 7 countries
Study dates
1 Jun 2018to Dec 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

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

Who cannot join

  • Participation in a trial with experimental drugs

Trial locations and contacts

13 sites in 7 countries. Contact the study team or a site near you to ask about taking part.

13 sites in 7 countries

Finland4 sites

  • Helsinki University Central Hospital

    Helsinki, Uusimaa, 00290

  • Oulu university hospital

    Oulu

  • Department of Oncology

    Tampere, Pirkanmaa, 33520

  • Turku university hospital

    Turku

Other trials in Finland

Sweden4 sites

  • Skone university hospital

    Lund

  • Karolinska University Hospital

    Stockholm

  • Sundsvall hospital

    Sundsvall

  • Uppsala academic hospital

    Uppsala

Other trials in Sweden

Denmark1 site

  • Odense University Hospital

    Odense

Other trials in Denmark

Iceland1 site

  • Landspitali

    Reykjavik

Other trials in Iceland

Ireland1 site

  • St. Vincents University Hospital

    Dublin

Other trials in Ireland

Netherlands1 site

  • Academic Medical Center

    Amsterdam

Other trials in Netherlands

Norway1 site

  • Haukeland University Hospital

    Bergen

Other trials in Norway

About this study

Official title: 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.

Read the 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.

Conditions
Solid Tumor
Being tested
Fluoropyrimidine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FluoropyrimidineDrug

    Also called S-1 / Teysuno, capecitabine, 5-fluorouracil, tegafur

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: After switch to and during one line of S-1 based chemotherapy (average 6 months)

Secondary outcomes (6)

  1. 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

    Measured: After switch to and during one line of another fluoropyrimidine regimen (average 6 months)

  2. 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

    Measured: During one line of fluoropyrimidine based chemotherapy (average 6 months)

  3. Diagnostic work-up

    Diagnostic work-up for cardiotoxicity in real world data

    Measured: During one line of fluoropyrimidine based chemotherapy (average 6 months)

  4. Time-lines for cardiotoxicity

    Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy

    Measured: During one line of fluoropyrimidine based chemotherapy (average 6 months)

  5. Dose-intensity

    Dose-intensity of the therapy at the cycle causing cardiotoxicity

    Measured: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity

  6. 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

    Measured: During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2020
  2. Study start1 Jun 2018
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04260269
Sponsor's protocol ID
R18045
Acronym
CardioSwitch
Status last verified
Dec 2024
First submitted
22 Jan 2020
Last updated
12 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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. No abstract available.

    PubMed 28623776

  • 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.

    PubMed 28286287

  • 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.

    PubMed 27181284

  • 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. doi: 10.3892/etm.2014.1576. Epub 2014 Feb 24.

    PubMed 24940424

  • 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.

    PubMed 19520246

  • 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.

    PubMed 23102544

  • 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.

    PubMed 23582737

  • Osterlund P, Kinos S, Pfeiffer P, Salminen T, Kwakman JJM, Frodin JE, Shah CH, Sorbye H, Ristamaki R, Halonen P, Soveri LM, Heerva E, Algars A, Barlund M, Hagman H, McDermott R, O'Reilly M, Rockert R, Liposits G, Kallio R, Flygare P, Teske AJ, van Werkhoven E, Punt CJA, Glimelius B. Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study. ESMO Open. 2022 Jun;7(3):100427. doi: 10.1016/j.esmoop.2022.100427. Epub 2022 Mar 30.

    PubMed 35798468

Questions about this trial

What is this clinical trial studying?

An observational study of Solid Tumor, run by Helsinki University Central Hospital at 13 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Finland, Sweden, Denmark, Iceland, Ireland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04260269, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in