- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02571894
The Cardio-Oncology Breast Cancer Study (COBC)
Effects of Identifying and Treating Early, Subclinical Cardiotoxicity on the Long-Term Incidence of Clinical Cardiotoxicity in Women With Breast Cancer, A Prospective Randomized Study: The Cardio-Oncology Breast Cancer Study (COBC)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Rationale for the study:
Breast cancer is the most common cancer among Swedish women, accounting for a third of all cancer cases among females. The breast cancer incidence has increased from 2596 to more than 8000 breast cancer diagnosis 2011. During the past 40 years, the age-adjusted incidence has doubled. Early adjuvant therapy reduces the risk of dying with about 50%. (Early adjuvant therapies; chemotherapy, antibodies, endocrine therapy, and radiotherapy). Treatment advances have improved survival rates, but treatment-related cardiotoxicity (CT) remains a substantial problem.
In general, earlier treatment of cardiotoxicity offers the best chances of preventing or ameliorating clinical cardiotoxicity. Risk factors should be modified or reduced by treating elevated blood pressure, normalizing lipids, encouraging weight reduction and smoking cessation. Patient-tailored therapy is now possible, especially given the availability of different chemotherapy regimens, safer anthracycline analogs such as liposomal doxorubicin, and cardioprotective medications such as angiotensin converting enzyme (ACE)-inhibitors, angiotensin receptor blockers, and b-blockers. It is now suggested that new cardiac biomarkers and ultrasound techniques can detect cardiotoxicity in its early, subclinical, stages. The investigators hypothesized that biomarkers can be used to detect subclinical cardiotoxicity and that detecting early signs of cardiotoxicity might reduce the number, time-to-onset, and severity of cardiotoxic events.
In present proposal the investigators aim in a randomized study to compare primary cardiac preventive measurements versus standard care.
Objectives of the trial:
- Primary objective In a randomized study to investigate the cumulative incidence of cardiotoxic events, per randomized arm, before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy.
- Secondary Objectives To compare the number, time-to-onset, and severity of cardiotoxic events in an experimental group assessed and treated for subclinical cardiotoxicity before start of chemotherapy, during treatment and at 1, 5, and 10 years after the completion of the chemotherapy and a control group receiving standard of care without early assessment for subclinical cardiotoxicity. Data on the same variables will be collected from both groups before start of chemotherapy, during treatment and at 1, 5, and 10 years. Data from the experimental group will be used in real time to guide therapy, but data from the control group will be not be analyzed until after the end of the study.
To assess subclinical cardiotoxicity with serum concentrations of biomarkers, tissue Doppler and strain echocardiography, electrocardiography, and magnetic resonance imaging, as well as with standard cardiac risk assessment based on standard risk factors: a history of heart disease, increasing age, obesity, hypertension, diabetes mellitus, hypercholesterolemia, smoking, parasternal radiotherapy, and the cumulative dose of anthracyclines and trastuzumab.
To assess the association between primary treatment of existing standard cardiac risk factors, biomarkers and parameters of echocardiography, electrocardiography, and cardiac magnetic resonance imaging, (predictors) and subsequent occurrence of clinical or subclinical cardiotoxicity of cardiotoxicity (outcome) within and between-groups, over time.
To examine how a diagnosis of breast cancer and the development of cardiotoxicity influences women's quality of life.
Tipo de estudio
Inscripción (Anticipado)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Stockholm, Suecia, 171 76
- Karolinska University Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Women with newly diagnosed breast cancer who are eligible to receive neo-adjuvant or adjuvant chemotherapy, with or without trastuzumab, according to the guidelines for breast cancer.
- Written informed consent must be given.
Exclusion Criteria:
- A history of heart disease; ischemic heart disease, arrhythmias, heart failure, and valve diseases.
- Previously received oncological treatment for any malignancy.
- Other disease or conditions that complicates or precludes the patient from following the study protocol.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Sin intervención: Observational arm
Participants randomized to observational arm will receive standard oncological followup and care.
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Experimental: Intervention arm
Intervention arm receives standard oncological followup and care + subclinical cardiotoxicity surveillance and treatment.
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Intervention arm receives cardiology assessment and intervention.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Event free survival
Periodo de tiempo: 1 year after the completion of the chemotherapy.
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The cumulative incidence of clinical or subclinical cardiotoxicity, per randomized arm, in women with breast cancer at 1 year after treatment with neo- or adjuvant chemotherapy.
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1 year after the completion of the chemotherapy.
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
Event free survival
Periodo de tiempo: 5 and 10 years after the completion of the chemotherapy.
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5 and 10 years after the completion of the chemotherapy.
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Overall survival
Periodo de tiempo: 1, 5 and 10 years after the completion of the chemotherapy.
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1, 5 and 10 years after the completion of the chemotherapy.
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The levels of serum biomarkers (hs-Troponin T (hs-TnT), B-type natriuretic peptide (BNP)).
Periodo de tiempo: 1, 5 and 10 years after the completion of the chemotherapy.
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1, 5 and 10 years after the completion of the chemotherapy.
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Echocardiographic global longitudinal strain
Periodo de tiempo: 1, 5 and 10 years after the completion of the chemotherapy.
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1, 5 and 10 years after the completion of the chemotherapy.
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The quality of life
Periodo de tiempo: 1, 5 and 10 years after the completion of the chemotherapy.
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1, 5 and 10 years after the completion of the chemotherapy.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Elham Hedayati, MD, PhD, Karolinska University Hospital
- Investigador principal: Laila Hubbert, MD, PhD, University Hospital, Linkoeping
Publicaciones y enlaces útiles
Publicaciones Generales
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- Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller M, Franzini L, Williams A, de Haes HC, Hopwood P, Cull A, Aaronson NK. The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncol. 1996 Oct;14(10):2756-68. doi: 10.1200/JCO.1996.14.10.2756.
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- EBCTCG (Early Breast Cancer Trialists' Collaborative Group); McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, Gray R, Mannu G, Peto R, Whelan T, Wang Y, Wang Z, Darby S. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014 Jun 21;383(9935):2127-35. doi: 10.1016/S0140-6736(14)60488-8. Epub 2014 Mar 19. Erratum In: Lancet. 2014 Nov 22;384(9957):1848.
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44. doi: 10.1016/S0140-6736(11)61625-5. Epub 2011 Dec 5.
- Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Kohne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. doi: 10.1016/S0140-6736(13)61094-6. Epub 2013 Jul 18.
- Oberholzer K, Kunz RP, Dittrich M, Thelen M. [Anthracycline-induced cardiotoxicity: cardiac MRI after treatment for childhood cancer]. Rofo. 2004 Sep;176(9):1245-50. doi: 10.1055/s-2004-813416. German.
- Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, Plana JC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014 Mar 4;63(8):809-16. doi: 10.1016/j.jacc.2013.10.061. Epub 2013 Nov 27. Erratum In: J Am Coll Cardiol. 2016 Mar 22;67(11):1385.
- Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol. 2007 Sep 1;25(25):3859-65. doi: 10.1200/JCO.2006.09.1611. Epub 2007 Jul 23.
- Verma S, Ewer MS. Is cardiotoxicity being adequately assessed in current trials of cytotoxic and targeted agents in breast cancer? Ann Oncol. 2011 May;22(5):1011-1018. doi: 10.1093/annonc/mdq607. Epub 2010 Nov 22.
- Ewer MS, Swain SM, Cardinale D, Fadol A, Suter TM. Cardiac dysfunction after cancer treatment. Tex Heart Inst J. 2011;38(3):248-52.
- Harbeck N, Ewer MS, De Laurentiis M, Suter TM, Ewer SM. Cardiovascular complications of conventional and targeted adjuvant breast cancer therapy. Ann Oncol. 2011 Jun;22(6):1250-1258. doi: 10.1093/annonc/mdq543. Epub 2010 Nov 26.
- Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, Martino S, Gralow JR, Dakhil SR, Ingle JN, Winer EP, Gelmon KA, Gersh BJ, Jaffe AS, Rodeheffer RJ. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008 Mar 10;26(8):1231-8. doi: 10.1200/JCO.2007.13.5467. Epub 2008 Feb 4.
- Nilsson G, Holmberg L, Garmo H, Duvernoy O, Sjogren I, Lagerqvist B, Blomqvist C. Distribution of coronary artery stenosis after radiation for breast cancer. J Clin Oncol. 2012 Feb 1;30(4):380-6. doi: 10.1200/JCO.2011.34.5900. Epub 2011 Dec 27.
- Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography - basic concepts and clinical applicability. Curr Cardiol Rev. 2009 May;5(2):133-48. doi: 10.2174/157340309788166642.
- Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T, Tian G, Kirkpatrick ID, Singal PK, Krahn M, Grenier D, Jassal DS. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011 May 31;57(22):2263-70. doi: 10.1016/j.jacc.2010.11.063.
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- Goetze JP, Alehagen U, Flyvbjerg A, Rehfeld JF. Making sense of chromogranin A in heart disease. Lancet Diabetes Endocrinol. 2013 Sep;1(1):7-8. doi: 10.1016/S2213-8587(13)70035-4. Epub 2013 Jun 13. No abstract available.
- Chisalita SI, Dahlstrom U, Arnqvist HJ, Alehagen U. Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors. Eur J Endocrinol. 2011 Dec;165(6):891-8. doi: 10.1530/EJE-11-0584. Epub 2011 Oct 5.
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- Bozkurt B, Mann DL, Deswal A. Biomarkers of inflammation in heart failure. Heart Fail Rev. 2010 Jul;15(4):331-41. doi: 10.1007/s10741-009-9140-3.
- Tarantini L, Cioffi G, Gori S, Tuccia F, Boccardi L, Bovelli D, Lestuzzi C, Maurea N, Oliva S, Russo G, Faggiano P; Italian Cardio-Oncologic Network. Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail. 2012 Feb;18(2):113-9. doi: 10.1016/j.cardfail.2011.10.015. Epub 2011 Dec 3.
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Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Trastornos inducidos químicamente
- Procesos Patológicos
- Enfermedades cardíacas
- Enfermedades cardiovasculares
- Enfermedades de la piel
- Neoplasias
- Neoplasias por sitio
- Heridas y Lesiones
- Enfermedades de los senos
- Efectos secundarios y reacciones adversas relacionados con los medicamentos
- Lesiones por radiación
- Neoplasias de mama
- Miocardiopatías
- Cardiotoxicidad
Otros números de identificación del estudio
- COBC
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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