Chemotherapy With or Without Isolated Hepatic Perfusion With Melphalan in Treating Patients With Colorectal Cancer That Has Spread to the Liver
A Phase III Prospective Random Assignment Trial of Regional and Systemic Chemotherapy With or Without Initial Isolated Hepatic Perfusion for Patients With Metastatic Unresectable Colorectal Cancers of the Liver
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells. It is not yet known which chemotherapy regimen is most effective for colorectal cancer that has spread to the liver.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without isolated hepatic perfusion with melphalan in treating patients who have colorectal cancer that has spread to the liver.
Visão geral do estudo
Status
Condições
Descrição detalhada
OBJECTIVES:
- Compare the disease-free and overall survival of patients with unresectable colorectal cancer metastatic to the liver treated with regional and systemic chemotherapy with or without isolated hepatic perfusion with melphalan.
- Compare the response rate and duration of response in patients treated with these regimens.
- Compare the patterns of recurrence (liver vs systemic) in patients treated with these regimens.
- Compare the health-related quality of life (QOL) of patients treated with these regimens.
- Determine whether baseline QOL correlates with length of survival of patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy for liver metastasis (yes vs no) and percentage of hepatic replacement (less than 25% vs at least 25%). All patients undergo laparotomy to determine final eligibility. Eligible patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo hyperthermic isolated hepatic perfusion with melphalan over 60 minutes. Patients then undergo placement of an intrahepatic pump or port. At 6 weeks post hepatic perfusion, patients receive systemic chemotherapy comprising irinotecan IV over 90 minutes on day 1 followed by fluorouracil IV over 15 minutes and leucovorin calcium (CF) IV over 15 minutes on days 1-3. Patients receive local chemotherapy comprising floxuridine (FUDR) and CF by hepatic arterial infusion (HAI) continuously on days 14-28.
- Arm II: Patients undergo placement of an intrahepatic pump or port at laparotomy. At 7 days post laparotomy, patients receive FUDR and CF by HAI continuously for 14 days. Beginning 2 weeks after completion of HAI, patients receive systemic and local chemotherapy as in arm I.
Treatment with combined systemic and local chemotherapy repeats every 35 days for a maximum of 6 courses. Treatment with local chemotherapy alone repeats every 28 days for a maximum of 6 additional courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, postoperatively, every third course of chemotherapy, every 3 months for 2 years, and then every 6 months thereafter.
Patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 168 patients (84 per treatment arm) will be accrued for this study within 54 months.
Tipo de estudo
Estágio
- Fase 3
Contactos e Locais
Locais de estudo
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Maryland
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Bethesda, Maryland, Estados Unidos, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed metastatic colorectal cancer of the parenchyma of the liver
- No evidence of extrahepatic disease (limited resectable extrahepatic disease allowed)
Unresectable liver metastasis, as defined by the following:
- More than 3 sites of disease
- Bilobar disease
- Tumor abutting major vascular or ductal structures
- Measurable disease
- No biopsy-proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices, or collateral vessels around organs drained by the portal venous system
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Platelet count greater than 100,000/mm^3
- Hematocrit greater than 27.0%
- WBC greater than 3,000/mm^3
Hepatic:
- Bilirubin less than 2.0 mg/dL
- PT no greater than 2 seconds over upper limit of normal
- Elevations in transaminases secondary to metastatic disease allowed
- No veno-occlusive disease
No active chronic hepatitis
- Hepatitis B or C allowed provided there is no evidence of cirrhosis
Renal:
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- No ischemic cardiac disease
- No prior congestive heart failure with LVEF less than 40%
Pulmonary:
- No chronic obstructive pulmonary disease or other chronic pulmonary disease with pulmonary function test less than 50% of predicted
Other:
- No active infections
- Not pregnant or nursing
- Negative pregnancy test
- Weight greater than 30 kg
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 weeks since prior biologic therapy for disease and recovered
Chemotherapy:
- At least 4 weeks since prior chemotherapy for disease and recovered
- No prior intrahepatic artery infusion therapy with floxuridine
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 4 weeks since prior radiotherapy for disease and recovered
Surgery:
- Not specified
Other:
- No concurrent immunosuppressive drugs
- No concurrent chronic anticoagulants
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
Colaboradores e Investigadores
Patrocinador
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do aparelho digestivo
- Neoplasias
- Neoplasias por local
- Neoplasias gastrointestinais
- Neoplasias do Aparelho Digestivo
- Doenças Gastrointestinais
- Doenças do cólon
- Doenças Intestinais
- Neoplasias Intestinais
- Doenças retais
- Neoplasias Colorretais
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes de proteção
- Agentes Antineoplásicos Alquilantes
- Agentes Alquilantes
- Agonistas Mieloablativos
- Inibidores da Topoisomerase
- Micronutrientes
- Vitaminas
- Hormônios e Agentes Reguladores de Cálcio
- Inibidores da Topoisomerase I
- Antídotos
- Complexo de Vitamina B
- Fluorouracil
- Leucovorina
- Irinotecano
- Cálcio
- Levoleucovorina
- Melfalano
- Floxuridina
Outros números de identificação do estudo
- 010093
- NCI-01-C-0093
- CDR0000068562
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