Ignite Creation Date:
2025-12-24 @ 11:10 PM
Ignite Modification Date:
2026-01-01 @ 4:33 AM
Study NCT ID:
NCT04260269
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-12-12
First Post:
2020-01-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C079198', 'term': 'S 1 (combination)'}, {'id': 'C586502', 'term': 'tegafur-gimeracil-oteracil'}, {'id': 'D000069287', 'term': 'Capecitabine'}, {'id': 'D005472', 'term': 'Fluorouracil'}, {'id': 'D005641', 'term': 'Tegafur'}, {'id': 'C000613803', 'term': 'trifluridine tipiracil drug combination'}], 'ancestors': [{'id': 'D003841', 'term': 'Deoxycytidine'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D014498', 'term': 'Uracil'}, {'id': 'D011744', 'term': 'Pyrimidinones'}, {'id': 'D003853', 'term': 'Deoxyribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'ENROLLING_BY_INVITATION', 'startDateStruct': {'date': '2018-06-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-12', 'completionDateStruct': {'date': '2027-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-12-07', 'studyFirstSubmitDate': '2020-01-22', 'studyFirstSubmitQcDate': '2020-02-05', 'lastUpdatePostDateStruct': {'date': '2024-12-12', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Recurrence of fluoropyrimidine related cardiac toxicity after switch to S-1 based treatment', 'timeFrame': 'After switch to and during one line of S-1 based chemotherapy (average 6 months)', 'description': 'Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to S-1'}], 'secondaryOutcomes': [{'measure': 'Recurrence of fluoropyrimidine related cardiac toxicity after switch to any fluoropyrimidine', 'timeFrame': 'After switch to and during one line of another fluoropyrimidine regimen (average 6 months)', 'description': 'Cardiac tolerability according to NCI-CTCAE following cardiotoxicity initiated switch of fluoropyrimidine to another fluoropyrimidine chemotherapy'}, {'measure': 'Cardiac symptoms during fluoropyrimidine chemotherapy', 'timeFrame': 'During one line of fluoropyrimidine based chemotherapy (average 6 months)', 'description': 'Frequency and severity according to NCI-CTCAE of cardiac symptoms during different fluoropyrimidines and the correlation with other added cytotoxics or biologics'}, {'measure': 'Diagnostic work-up', 'timeFrame': 'During one line of fluoropyrimidine based chemotherapy (average 6 months)', 'description': 'Diagnostic work-up for cardiotoxicity in real world data'}, {'measure': 'Time-lines for cardiotoxicity', 'timeFrame': 'During one line of fluoropyrimidine based chemotherapy (average 6 months)', 'description': 'Time-lines for appearance of cardiotoxicity during fluoropyrimidine-based chemotherapy'}, {'measure': 'Dose-intensity', 'timeFrame': 'During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity', 'description': 'Dose-intensity of the therapy at the cycle causing cardiotoxicity'}, {'measure': 'Alteration in cardiac functional parameters during fluoropyrimidine treatment induced cardiotoxicity', 'timeFrame': 'During one cycle (average 3 weeks) of fluoropyrimidine-based chemotherapy causing cardiac toxicity', 'description': 'The alterations of (if evaluated), graded as normal, non-significant abnormalities or significant abnormalities.:\n\n* ECG abnormalities\n* Ejection fraction in %\n* Coronary artery status on angiogram\n* Cardiac arrhythmias in ECG, Holter or cardiac monitor registration\n* Plasma troponin concentration and other cardiac enzymes and other laboratory tests as within reference range ro abnormal\n* Serum alpha-fluoro-beta-alanine (FBAL) concentration'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Solid Tumor']}, 'referencesModule': {'references': [{'pmid': '28623776', 'type': 'BACKGROUND', '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. No abstract available.'}, {'pmid': '28286287', 'type': 'BACKGROUND', '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.'}, {'pmid': '27181284', 'type': 'BACKGROUND', '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.'}, {'pmid': '24940424', 'type': 'BACKGROUND', '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. doi: 10.3892/etm.2014.1576. Epub 2014 Feb 24.'}, {'pmid': '19520246', 'type': 'BACKGROUND', '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.'}, {'pmid': '23102544', 'type': 'BACKGROUND', 'citation': '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': '23582737', 'type': 'BACKGROUND', '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.'}, {'pmid': '35798468', 'type': 'DERIVED', 'citation': "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."}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nAnecdotal 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'All consecutive patients who fulfil the following inclusion criteria will be included in the database until the target number of patients has been included:\n\n* Solid tumor\n* Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment\n* Re-challenge with a different fluoropyrimidine-based treatment. Primary endpoint is switch to S-1 and secondary any fluoropyrimidine population.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Solid tumor\n* Cardiotoxicity grade 1-4 during fluoropyrimidine-based treatment\n* Re-challenge with a different fluoropyrimidine-based therapy\n\nExclusion Criteria:\n\n• Participation in a trial with experimental drugs'}, 'identificationModule': {'nctId': 'NCT04260269', 'acronym': 'CardioSwitch', 'briefTitle': 'Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity Study', 'organization': {'class': 'OTHER', 'fullName': 'Helsinki University Central Hospital'}, 'officialTitle': 'Feasibility of Switching Fluoropyrimidine Due to Cardiotoxicity in Patients with Solid Tumors: a Retrospective, International and Non-interventional Study', 'orgStudyIdInfo': {'id': 'R18045'}}, 'armsInterventionsModule': {'interventions': [{'name': 'Fluoropyrimidine', 'type': 'DRUG', 'otherNames': ['S-1 / Teysuno', 'capecitabine', '5-fluorouracil', 'tegafur', 'trifluridine-tipiracil / Lonsurf'], 'description': '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.\n\nThis 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.\n\nCardiac 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.'}]}, 'contactsLocationsModule': {'locations': [{'city': 'Odense', 'country': 'Denmark', 'facility': 'Odense University Hospital', 'geoPoint': {'lat': 55.39594, 'lon': 10.38831}}, {'zip': '33520', 'city': 'Tampere', 'state': 'Pirkanmaa', 'country': 'Finland', 'facility': 'Department of Oncology', 'geoPoint': {'lat': 61.49911, 'lon': 23.78712}}, {'zip': '00290', 'city': 'Helsinki', 'state': 'Uusimaa', 'country': 'Finland', 'facility': 'Helsinki University Central Hospital', 'geoPoint': {'lat': 60.16952, 'lon': 24.93545}}, {'city': 'Oulu', 'country': 'Finland', 'facility': 'Oulu university hospital', 'geoPoint': {'lat': 65.01236, 'lon': 25.46816}}, {'city': 'Turku', 'country': 'Finland', 'facility': 'Turku university hospital', 'geoPoint': {'lat': 60.45148, 'lon': 22.26869}}, {'city': 'Reykjavik', 'country': 'Iceland', 'facility': 'Landspitali', 'geoPoint': {'lat': 64.13548, 'lon': -21.89541}}, {'city': 'Dublin', 'country': 'Ireland', 'facility': 'St. Vincents University Hospital', 'geoPoint': {'lat': 53.33306, 'lon': -6.24889}}, {'city': 'Amsterdam', 'country': 'Netherlands', 'facility': 'Academic Medical Center', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}, {'city': 'Bergen', 'country': 'Norway', 'facility': 'Haukeland University Hospital', 'geoPoint': {'lat': 60.39299, 'lon': 5.32415}}, {'city': 'Lund', 'country': 'Sweden', 'facility': 'Skone university hospital', 'geoPoint': {'lat': 55.70584, 'lon': 13.19321}}, {'city': 'Stockholm', 'country': 'Sweden', 'facility': 'Karolinska University Hospital', 'geoPoint': {'lat': 59.32938, 'lon': 18.06871}}, {'city': 'Sundsvall', 'country': 'Sweden', 'facility': 'Sundsvall hospital', 'geoPoint': {'lat': 62.39129, 'lon': 17.3063}}, {'city': 'Uppsala', 'country': 'Sweden', 'facility': 'Uppsala academic hospital', 'geoPoint': {'lat': 59.85882, 'lon': 17.63889}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Helsinki University Central Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Tampere University Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor Oncology', 'investigatorFullName': 'Pia Osterlund', 'investigatorAffiliation': 'Tampere University Hospital'}}}}