Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer

22 de enero de 2013 actualizado por: University of Southampton

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

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

Intervencionista

Inscripción (Anticipado)

340

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Louisa Little
  • Número de teléfono: 02380795154

Ubicaciones de estudio

    • England
      • Basildon, England, Reino Unido, SS16 5NL
        • Reclutamiento
        • Basildon University Hospital
        • Contacto:
          • Pauline Leonard, MD
          • Número de teléfono: 44-1702-435-555
      • 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
      • Bournemouth, England, Reino Unido, BH7 7DW
        • Reclutamiento
        • Royal Bournemouth Hospital
        • Contacto:
      • Cambridge, England, Reino Unido, CB2 0QQ
        • Reclutamiento
        • Addenbrooke's Hospital
        • Contacto:
      • Guildford, England, Reino Unido, GU2 7XX
        • Reclutamiento
        • St. Luke's Cancer Centre at Royal Surrey County Hospital
        • Contacto:
          • Sharadah Essapen, MD
          • Número de teléfono: 44-1483-571-122
      • Liverpool, England, Reino Unido, L9 7AL
        • Reclutamiento
        • Aintree University Hospital
        • Contacto:
      • Liverpool, England, Reino Unido, L9 7AL
        • Reclutamiento
        • Royal Liverpool University Hospital
        • Contacto:
          • Paula Ghaneh, MD
      • London, England, Reino Unido, SW3 6JJ
        • Reclutamiento
        • Royal Marsden - London
        • Contacto:
          • David Cunningham, MD
          • Número de teléfono: 44-20-8661-3156
      • London, England, Reino Unido, EC1A 7BE
        • Reclutamiento
        • Saint Bartholomew's Hospital
      • London, England, Reino Unido, W6 8RF
        • Reclutamiento
        • Charing Cross Hospital
        • Contacto:
      • London, England, Reino Unido, NW3 2PF
        • Reclutamiento
        • UCL Cancer Institute
        • Contacto:
          • Astrid Mayer, MD
          • Número de teléfono: 44-207-794-0500
          • Correo electrónico: a.mayer@ucl.ac.uk
      • Merseyside, England, Reino Unido, CH63 4JY
        • Reclutamiento
        • Clatterbridge Centre for Oncology
      • Newport, England, Reino Unido, PO30 5TG
        • Reclutamiento
        • St. Mary's Hospital
        • Contacto:
          • Christopher Baughan, MD
          • Número de teléfono: 44-1983-524-081
      • Nottingham, England, Reino Unido, NG5 1PB
        • Reclutamiento
        • Cancer Research Centre at Weston Park Hospital
        • Contacto:
          • J. Hornbuckle, MD
          • Número de teléfono: 44-115-969-1169 ext. 47599
      • Poole Dorset, England, Reino Unido, BH15 2JB
        • Reclutamiento
        • Dorset Cancer Centre
        • Contacto:
          • Tamas Hickish, MD
          • Número de teléfono: 44-1202-442-532
      • Salisbury, England, Reino Unido, SP2 8BJ
        • Reclutamiento
        • Salisbury District Hospital
      • Southampton, England, Reino Unido, SO16 6YD
        • Reclutamiento
        • Southampton General Hospital
        • Contacto:
      • Sutton, England, Reino Unido, SM2 5PT
        • Reclutamiento
        • Royal Marsden - Surrey
      • Westcliff-On-Sea, England, Reino Unido, SS0 0RY
        • Reclutamiento
        • Southend University Hospital NHS Foundation Trust
        • Contacto:
          • Pauline Leonard, MD
          • Número de teléfono: 44-1702-435-555
      • Worthing, England, Reino Unido, BN11 2DH
        • Reclutamiento
        • Worthing Hospital
        • Contacto:
          • Andrew Webb, MD
          • Número de teléfono: 44-1903-205-111
    • Wales
      • Cardiff, Wales, Reino Unido, CF14 2TL
        • Reclutamiento
        • Velindre Cancer Center at Velindre Hospital
        • Contacto:
          • Timothy Maughan, MD
          • Número de teléfono: 44-2920-316-904
      • Cardiff, Wales, Reino Unido, CF14 4XW
        • Reclutamiento
        • University Hospital of Wales
        • Contacto:
          • Timothy Maughan, MD
          • Número de teléfono: 44-2920-316-904

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

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

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Investigadores

  • Silla de estudio: John N. Primrose, MD, University Hospital Southampton NHS Foundation Trust

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de febrero de 2007

Finalización primaria (Anticipado)

1 de diciembre de 2014

Fechas de registro del estudio

Enviado por primera vez

4 de junio de 2007

Primero enviado que cumplió con los criterios de control de calidad

4 de junio de 2007

Publicado por primera vez (Estimar)

5 de junio de 2007

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

23 de enero de 2013

Última actualización enviada que cumplió con los criterios de control de calidad

22 de enero de 2013

Última verificación

1 de abril de 2008

Más información

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. .

Ensayos clínicos sobre Cáncer colonrectal

Ensayos clínicos sobre fluorouracilo

3
Suscribir