Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study

NCT04260269 | Enrolling By Invitation

• 1 other identifier: R18045
• Study Type: observational
• Target: 200
• Locations: 7 countries
• Sites: 13

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (6)

• 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 symptoms during fluoropyrimidine chemotherapy

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

• Diagnostic work-up

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

• Time-lines for cardiotoxicity

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

• Dose-intensity

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

Interventions

Fluoropyrimidine DRUG

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.

Also known as: S-1 / Teysuno, capecitabine, 5-fluorouracil, tegafur, trifluridine-tipiracil / Lonsurf

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Participation in a trial with experimental drugs

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Tampere University Hospital: collaborator

Study Sites (13)

Odense University Hospital

Odense, Denmark

Location

Department of Oncology

Tampere, Pirkanmaa, 33520, Finland

Location

Helsinki University Central Hospital

Helsinki, Uusimaa, 00290, Finland

Location

Oulu university hospital

Oulu, Finland

Location

Turku university hospital

Turku, Finland

Location

Landspitali

Reykjavik, Iceland

Location

St. Vincents University Hospital

Dublin, Ireland

Location

Academic Medical Center

Amsterdam, Netherlands

Location

Haukeland University Hospital

Bergen, Norway

Location

Skone university hospital

Lund, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Sundsvall hospital

Sundsvall, Sweden

Location

Uppsala academic hospital

Uppsala, Sweden

Location

Related Publications (8)

• 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.

  PMID: 28623776 BACKGROUND

• 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.

  PMID: 28286287 BACKGROUND

• 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.

  PMID: 27181284 BACKGROUND

• 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.

  PMID: 24940424 BACKGROUND

• 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.

  PMID: 19520246 BACKGROUND

• 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.

  PMID: 23102544 BACKGROUND

• 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.

  PMID: 23582737 BACKGROUND

• 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.

  PMID: 35798468 DERIVED

MeSH Terms

Interventions

S 1 (combination); tegafur-gimeracil-oteracil; Capecitabine; Fluorouracil; Tegafur; trifluridine tipiracil drug combination

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Oncology

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: February 7, 2020
• Study Start: June 1, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); FI (4); DK (1); IE (1); IC (1); NO (1); SE (4)