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

22 de janeiro de 2013 atualizado 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.

Visão geral do estudo

Status

Desconhecido

Condições

Intervenção / Tratamento

Descrição detalhada

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 estudo

Intervencional

Inscrição (Antecipado)

340

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Reino Unido
    • England
      • Basildon, England, Reino Unido, SS16 5NL
        • Recrutamento
        • Basildon University Hospital
        • Contato:
          • Pauline Leonard, MD
          • Número de telefone: 44-1702-435-555
      • Basingstoke, England, Reino Unido, RG24 9NA
        • Recrutamento
        • Basingstoke and North Hampshire NHS Foundation Trust
        • Contato:
          • Charlotte Rees, MD
          • Número de telefone: 44-125-631-4793
      • Bournemouth, England, Reino Unido, BH7 7DW
        • Recrutamento
        • Royal Bournemouth Hospital
        • Contato:
      • Cambridge, England, Reino Unido, CB2 0QQ
      • Guildford, England, Reino Unido, GU2 7XX
        • Recrutamento
        • St. Luke's Cancer Centre at Royal Surrey County Hospital
        • Contato:
          • Sharadah Essapen, MD
          • Número de telefone: 44-1483-571-122
      • Liverpool, England, Reino Unido, L9 7AL
        • Recrutamento
        • Aintree University Hospital
        • Contato:
      • Liverpool, England, Reino Unido, L9 7AL
        • Recrutamento
        • Royal Liverpool University Hospital
        • Contato:
          • Paula Ghaneh, MD
      • London, England, Reino Unido, SW3 6JJ
        • Recrutamento
        • Royal Marsden - London
        • Contato:
          • David Cunningham, MD
          • Número de telefone: 44-20-8661-3156
      • London, England, Reino Unido, EC1A 7BE
        • Recrutamento
        • Saint Bartholomew's Hospital
      • London, England, Reino Unido, W6 8RF
        • Recrutamento
        • Charing Cross Hospital
        • Contato:
      • London, England, Reino Unido, NW3 2PF
        • Recrutamento
        • UCL Cancer Institute
        • Contato:
      • Merseyside, England, Reino Unido, CH63 4JY
        • Recrutamento
        • Clatterbridge Centre for Oncology
      • Newport, England, Reino Unido, PO30 5TG
        • Recrutamento
        • St. Mary's Hospital
        • Contato:
          • Christopher Baughan, MD
          • Número de telefone: 44-1983-524-081
      • Nottingham, England, Reino Unido, NG5 1PB
        • Recrutamento
        • Cancer Research Centre at Weston Park Hospital
        • Contato:
          • J. Hornbuckle, MD
          • Número de telefone: 44-115-969-1169 ext. 47599
      • Poole Dorset, England, Reino Unido, BH15 2JB
        • Recrutamento
        • Dorset Cancer Centre
        • Contato:
          • Tamas Hickish, MD
          • Número de telefone: 44-1202-442-532
      • Salisbury, England, Reino Unido, SP2 8BJ
        • Recrutamento
        • Salisbury District Hospital
      • Southampton, England, Reino Unido, SO16 6YD
        • Recrutamento
        • Southampton General Hospital
        • Contato:
      • Sutton, England, Reino Unido, SM2 5PT
        • Recrutamento
        • Royal Marsden - Surrey
      • Westcliff-On-Sea, England, Reino Unido, SS0 0RY
        • Recrutamento
        • Southend University Hospital NHS Foundation Trust
        • Contato:
          • Pauline Leonard, MD
          • Número de telefone: 44-1702-435-555
      • Worthing, England, Reino Unido, BN11 2DH
        • Recrutamento
        • Worthing Hospital
        • Contato:
          • Andrew Webb, MD
          • Número de telefone: 44-1903-205-111
    • Wales
      • Cardiff, Wales, Reino Unido, CF14 2TL
        • Recrutamento
        • Velindre Cancer Center at Velindre Hospital
        • Contato:
          • Timothy Maughan, MD
          • Número de telefone: 44-2920-316-904
      • Cardiff, Wales, Reino Unido, CF14 4XW
        • Recrutamento
        • University Hospital of Wales
        • Contato:
          • Timothy Maughan, MD
          • Número de telefone: 44-2920-316-904

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador Ativo: OxMdG / IrMdG chemotherapy
OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks
Medicamento: fluorouracil
Medicamento: leucovorina cálcica
Procedimento: Terapia adjuvante
Procedimento: terapia neoadjuvante
Medicamento: oxaliplatina
Procedimento: avaliação de qualidade de vida
Medicamento: capecitabina
Outro: estudo de variáveis ​​socioeconômicas e demográficas
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
Medicamento: fluorouracil
Medicamento: leucovorina cálcica
Procedimento: Terapia adjuvante
Procedimento: terapia neoadjuvante
Medicamento: oxaliplatina
Procedimento: avaliação de qualidade de vida
Medicamento: capecitabina
Outro: estudo de variáveis ​​socioeconômicas e demográficas
Biológico: cetuximabe

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
Progression-free survival
Prazo: end of study
end of study

Medidas de resultados secundários

Medida de resultado
Prazo
Sobrevida geral
Prazo: fim do estudo
fim do estudo
Response rate before surgery as assessed by RECIST criteria
Prazo: end of study
end of study
Pathological resection status
Prazo: end of study
end of study
Toxicity
Prazo: end of study
end of study
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
Prazo: end of study
end of study
Cost effectiveness
Prazo: end of study
end of study
Safety
Prazo: end of study
end of study

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

University of Southampton

Colaboradores

University Hospital Southampton NHS Foundation Trust

Investigadores

  • Cadeira de estudo: John N. Primrose, MD, University Hospital Southampton NHS Foundation Trust

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de fevereiro de 2007

Conclusão Primária (Antecipado)

1 de dezembro de 2014

Datas de inscrição no estudo

Enviado pela primeira vez

4 de junho de 2007

Enviado pela primeira vez que atendeu aos critérios de CQ

4 de junho de 2007

Primeira postagem (Estimativa)

5 de junho de 2007

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

23 de janeiro de 2013

Última atualização enviada que atendeu aos critérios de controle de qualidade

22 de janeiro de 2013

Última verificação

1 de abril de 2008

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • CDR0000549541
  • USCTU-4351
  • USCTU-EPOC
  • EUDRACT-2006-003121-82
  • ISRCTN22944367
  • EU-20732

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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