- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00482222
Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer
A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with monoclonal antibodies before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without cetuximab in treating liver metastases caused by colorectal cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without cetuximab before and after surgery in treating patients with resectable liver metastases caused by colorectal cancer.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Compare progression-free survival of patients with resectable colorectal liver metastases treated with neoadjuvant and adjuvant combination chemotherapy with vs without cetuximab.
Secondary
- Compare the overall survival of patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
- Compare the cost effectiveness of these regimens in these patients.
OUTLINE: This is a prospective, randomized, multicenter, open-label study. Patients are stratified according to participating center and assigned chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.
Neoadjuvant therapy:
Arm I: Patients receive 1 of the following chemotherapy regimens:
- OxMdG: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive 1 of the following regimens:
- OxMdG + cetuximab: Patients receive cetuximab IV over 1-2 hours on day 1 and OxMdG chemotherapy as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX + cetuximab: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and CAPOX chemotherapy as in arm I. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Surgery: Beginning 2-6 weeks after completion of chemotherapy, patients in both arms undergo liver resection.
Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive treatment (OxMdG or CAPOX with or without cetuximab) as in arm I or II of neoadjuvant therapy.
- Arm I: Treatment with OxMdG repeats every 2 weeks for up to 6 courses and treatment with CAPOX repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Treatment with OxMdG + cetuximab repeats every 2 weeks for up to 6 courses and treatment with CAPOX + cetuximab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 12 weeks during chemotherapy, at completion of study treatment, every 3 months for 1 year, and then every 6 months thereafter.
Cost per life year and per quality-adjusted life year is assessed at baseline, every 12 weeks during treatment, and then at 3, 5, and 10 years.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Louisa Little
- Número de teléfono: 02380795154
Ubicaciones de estudio
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England
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Basildon, England, Reino Unido, SS16 5NL
- Reclutamiento
- Basildon University Hospital
-
Contacto:
- Pauline Leonard, MD
- Número de teléfono: 44-1702-435-555
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Basingstoke, England, Reino Unido, RG24 9NA
- Reclutamiento
- Basingstoke and North Hampshire NHS Foundation Trust
-
Contacto:
- Charlotte Rees, MD
- Número de teléfono: 44-125-631-4793
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Bournemouth, England, Reino Unido, BH7 7DW
- Reclutamiento
- Royal Bournemouth Hospital
-
Contacto:
- Tamas Hickish, MD
- Número de teléfono: 44-1202-303-626
- Correo electrónico: tamas.hickish@rbch.nhs.uk
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Cambridge, England, Reino Unido, CB2 0QQ
- Reclutamiento
- Addenbrooke's Hospital
-
Contacto:
- Pippa Corrie, PhD, FRCP
- Número de teléfono: 44-1223-274-401
- Correo electrónico: pippa.corrie@addenbrookes.nhs.uk
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Guildford, England, Reino Unido, GU2 7XX
- Reclutamiento
- St. Luke's Cancer Centre at Royal Surrey County Hospital
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Contacto:
- Sharadah Essapen, MD
- Número de teléfono: 44-1483-571-122
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Liverpool, England, Reino Unido, L9 7AL
- Reclutamiento
- Aintree University Hospital
-
Contacto:
- Graeme J. Poston, MD
- Número de teléfono: 44-151-525-5980
- Correo electrónico: graeme.poston@aintree.nhs.uk
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Liverpool, England, Reino Unido, L9 7AL
- Reclutamiento
- Royal Liverpool University Hospital
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Contacto:
- Paula Ghaneh, MD
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London, England, Reino Unido, SW3 6JJ
- Reclutamiento
- Royal Marsden - London
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Contacto:
- David Cunningham, MD
- Número de teléfono: 44-20-8661-3156
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London, England, Reino Unido, EC1A 7BE
- Reclutamiento
- Saint Bartholomew's Hospital
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London, England, Reino Unido, W6 8RF
- Reclutamiento
- Charing Cross Hospital
-
Contacto:
- Charles P. Lowdell, MD, BSc, MBBS, FRCP, FRCR
- Número de teléfono: 44-208-383-0576
- Correo electrónico: charles.lowdell@imperial.nhs.uk
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London, England, Reino Unido, NW3 2PF
- Reclutamiento
- UCL Cancer Institute
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Contacto:
- Astrid Mayer, MD
- Número de teléfono: 44-207-794-0500
- Correo electrónico: a.mayer@ucl.ac.uk
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Merseyside, England, Reino Unido, CH63 4JY
- Reclutamiento
- Clatterbridge Centre for Oncology
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Newport, England, Reino Unido, PO30 5TG
- Reclutamiento
- St. Mary's Hospital
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Contacto:
- Christopher Baughan, MD
- Número de teléfono: 44-1983-524-081
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Nottingham, England, Reino Unido, NG5 1PB
- Reclutamiento
- Cancer Research Centre at Weston Park Hospital
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Contacto:
- J. Hornbuckle, MD
- Número de teléfono: 44-115-969-1169 ext. 47599
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Poole Dorset, England, Reino Unido, BH15 2JB
- Reclutamiento
- Dorset Cancer Centre
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Contacto:
- Tamas Hickish, MD
- Número de teléfono: 44-1202-442-532
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Salisbury, England, Reino Unido, SP2 8BJ
- Reclutamiento
- Salisbury District Hospital
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Southampton, England, Reino Unido, SO16 6YD
- Reclutamiento
- Southampton General Hospital
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Contacto:
- John N. Primrose, MD
- Número de teléfono: 44-23-8079-6144
- Correo electrónico: j.n.primrose@soton.ac.uk
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Sutton, England, Reino Unido, SM2 5PT
- Reclutamiento
- Royal Marsden - Surrey
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Westcliff-On-Sea, England, Reino Unido, SS0 0RY
- Reclutamiento
- Southend University Hospital NHS Foundation Trust
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Contacto:
- Pauline Leonard, MD
- Número de teléfono: 44-1702-435-555
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Worthing, England, Reino Unido, BN11 2DH
- Reclutamiento
- Worthing Hospital
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Contacto:
- Andrew Webb, MD
- Número de teléfono: 44-1903-205-111
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Wales
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Cardiff, Wales, Reino Unido, CF14 2TL
- Reclutamiento
- Velindre Cancer Center at Velindre Hospital
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Contacto:
- Timothy Maughan, MD
- Número de teléfono: 44-2920-316-904
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Cardiff, Wales, Reino Unido, CF14 4XW
- Reclutamiento
- University Hospital of Wales
-
Contacto:
- Timothy Maughan, MD
- Número de teléfono: 44-2920-316-904
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Histologically* or radiologically confirmed primary adenocarcinoma of the colon or rectum
- Advanced and/or metastatic disease NOTE: *Liver metastases should not be biopsied
Must have potentially resectable liver metastases present, as defined by any of the following:
- Metachronous metastases AND complete resection of the primary tumor without gross or microscopic evidence of residual disease (R0)
- Synchronous metastases AND R0 resection of the primary tumor > 1 month before study entry
- Synchronous metastases with sufficient evidence (e.g., by CT scan or diagnostic laparoscopy) that both the primary tumor and the liver metastases can be completely resected during the same procedure and resection of primary tumor can be delayed for 3-4 months
- Suboptimally resectable disease (i.e., potentially resectable disease with compromise of the resection margins)
- No detectable extrahepatic tumor that cannot be completely resected
- Unidimensionally measurable disease
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- WBC ≥ 4,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count > 150,000/mm³
- Bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 3 times ULN
- Creatinine clearance > 50 mL/min OR glomerular filtration rate > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- No psychiatric or neurological condition that would preclude study compliance
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No other prior or concurrent malignant disease that, in the opinion of the investigator, would preclude study treatment
- No concurrent severe uncontrolled medical illness (including poorly-controlled angina or myocardial infarction within the past 3 months) that would preclude study treatment
- No known hypersensitivity reaction to any of the components of the study drugs
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy for metastatic disease
- More than 6 months since prior adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, or irinotecan hydrochloride
- More than 1 month since prior rectal chemoradiotherapy comprising fluorouracil and leucovorin calcium
- No concurrent contraindicated medication
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador activo: OxMdG / IrMdG chemotherapy
OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks
|
|
Experimental: OxMdG / IrMdG chemotherapy with cetuximab
OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Progression-free survival
Periodo de tiempo: end of study
|
end of study
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
Sobrevivencia promedio
Periodo de tiempo: fin de estudio
|
fin de estudio
|
Response rate before surgery as assessed by RECIST criteria
Periodo de tiempo: end of study
|
end of study
|
Pathological resection status
Periodo de tiempo: end of study
|
end of study
|
Toxicity
Periodo de tiempo: end of study
|
end of study
|
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
Periodo de tiempo: end of study
|
end of study
|
Cost effectiveness
Periodo de tiempo: end of study
|
end of study
|
Safety
Periodo de tiempo: end of study
|
end of study
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: John N. Primrose, MD, University Hospital Southampton NHS Foundation Trust
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (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 (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Procesos Patológicos
- Neoplasias
- Neoplasias por sitio
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades Gastrointestinales
- Enfermedades del Colon
- Enfermedades intestinales
- Neoplasias Intestinales
- Enfermedades Rectales
- Procesos Neoplásicos
- Neoplasias colorrectales
- Metástasis de neoplasias
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes Protectores
- Agentes antineoplásicos inmunológicos
- Micronutrientes
- Vitaminas
- Hormonas y agentes reguladores del calcio
- Antídotos
- Complejo de vitamina B
- Fluorouracilo
- Capecitabina
- Oxaliplatino
- Leucovorina
- Calcio
- Levoleucovorina
- Cetuximab
Otros números de identificación del estudio
- CDR0000549541
- USCTU-4351
- USCTU-EPOC
- EUDRACT-2006-003121-82
- ISRCTN22944367
- EU-20732
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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