Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
5 de julho de 2017 atualizado por: Peter C. Enzinger, MD, Dana-Farber Cancer Institute
A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
The purpose of this research study is to determine if the combination of docetaxel, cisplatin, irinotecan and bevacizumab will help shrink metastatic esophageal or gastric cancer and how the cancer responds to this combination.
Bevacizumab is a new drug that is believed to stop the formation of new blood vessels that carry nutrients to tumors.
Bevacizumab is approved for use in metastatic colon and rectal cancer.
Docetaxel, cisplatin and irinotecan are traditional chemotherapy agents that have been tested together in another clinical trial for esophageal and gastric cancer.
It is hoped that adding bevacizumab to this regimen will make the treatment more effective.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
OBJECTIVES:
Primary
To determine the 10-month progression-free survival rate for the combination of TPC and Bevacizumab in patients with metastatic esophageal or gastric cancer
Secondary
- To determine the response rate (RECIST) and median duration of response
- To determine overall survival
- To determine toxicity
Exploratory
- To explore if 7/7 and 7/6 UGT1A1 polymorphisms correlate with grade III/IV irinotecan-related diarrhea and neutropenia when irinotecan is given at relatively low dose to patients with esophageal and gastric cancer
- To correlate expression of tumoral and serum VEGF with response and survival
- To correlate TGF alpha levels and tumor microvessel density with clinical activity
- To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab
DESIGN This trial will use a single stage design to differentiate a >/= 50% rate of 10-month progression-free survival from a </= 30% rate. The proposed regimen would be promising if at least 15 of 35 patients were alive and progression-free at 10 months.
Tipo de estudo
Intervencional
Inscrição (Real)
38
Estágio
- Fase 2
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
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Estados Unidos, 02115
- Beth Israel Deaconess Medical Center
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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
Inclusion Criteria:
- Histologically confirmed, unresectable esophageal or gastric carcinoma (carcinoma=adenocarcinoma or squamous cell carcinoma)
- Measurable disease greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan or 2 cm or greater by other radiographic technique
- Lesions must be measurable in at least one dimension
- Bone lesions, ascites, and effusions are not measurable
- 18 years of age or older
- ECOG performance status 0 or 1
- Life expectancy of at least 12 weeks
- Adequate bone marrow function
- Adequate renal function
- Adequate liver function
Exclusion Criteria:
- Prior chemotherapy (except as part of pre- or post-operative therapy, completed more than 1 year prior to start day of this protocol)
- History of severe hypersensitivity to bevacizumab, docetaxel, cisplatin, irinotecan, or drugs formulated with polysorbate 80
- Current, recent (within 4 weeks) or planned participation in an experimental drug study
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies within 7 days prior to Day 0 of study
- Myocardial infarction or stroke in past 6 months
- Blood pressure of > 150/100 mmHg
- Unstable angina
- New York Heart Association (NYHA) grade II or greater congestive heart failure
- Clinically significant peripheral vascular disease
- Persistent bleeding from primary tumor, while off anticoagulants, requiring repeated transfusions
- Evidence of bleeding diathesis or coagulopathy
- Uncontrolled serious medical or psychiatric illness
- Uncontrolled diarrhea
- Peripheral neuropathy > grade 1
- Clinically apparent central nervous system metastases or carcinomatous meningitis
- Other active malignancy other than non-melanoma skin cancer or in situ cervical carcinoma.
- Urine protein: creatinine ratio of 1.0 or greater at screening
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
- Serious non-healing wound, ulcer, or bone fracture
- Pregnant or breast-feeding
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: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA)
Patients received bevacizumab 10 mg/kg IV on day 1 every 3 weeks while on study.
Additionally, they received docetaxel 30 mg/m2 IV over 30 minutes, followed by cisplatin 25 mg/m2 IV over 30 minutes, followed by irinotecan 50 mg/m2 IV over 30 minutes on days 1 and 8 of each 3-week cycle until disease progression or unacceptable toxicity.
Dose reductions were not permitted for bevacizumab although treatment could be held up to 2 months.
If bevacizumab was discontinued, treatment with other agents could continue.
When docetaxel, cisplatin, or irinotecan was held on day 1 of a cycle, all agents were held.
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Outros nomes:
Outros nomes:
Outros nomes:
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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10-month Progression-Free Survival Rate
Prazo: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months.
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10-month progression-free survival rate is the probability of patients remaining alive and progression-free at 10-months from study entry estimated using Kaplan-Meier methods.
Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
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Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Best Response
Prazo: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
Both require confirmation no fewer than 4 weeks apart.
CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Stable disease is defined as any condition not meeting above criteria.
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Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Overall Survival
Prazo: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
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Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods.
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Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
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Progression-Free Survival
Prazo: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death.
Patients alive and progression-free at last follow-up are censored.
Per RECIST 1.0 criteria: progressive disease is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
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Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Peter Enzinger, MD, Dana-Farber Cancer Institute
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 setembro de 2006
Conclusão Primária (Real)
1 de novembro de 2008
Conclusão do estudo (Real)
1 de outubro de 2016
Datas de inscrição no estudo
Enviado pela primeira vez
31 de outubro de 2006
Enviado pela primeira vez que atendeu aos critérios de CQ
31 de outubro de 2006
Primeira postagem (Estimativa)
1 de novembro de 2006
Atualizações de registro de estudo
Última Atualização Postada (Real)
1 de agosto de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
5 de julho de 2017
Última verificação
1 de julho de 2017
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 Estômago
- Neoplasias do Estômago
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Moduladores de Tubulina
- Agentes Antimitóticos
- Moduladores de Mitose
- Inibidores da Topoisomerase
- Agentes Antineoplásicos Imunológicos
- Inibidores de angiogênese
- Agentes Moduladores da Angiogênese
- Substâncias de crescimento
- Inibidores de crescimento
- Inibidores da Topoisomerase I
- Docetaxel
- Cisplatina
- Bevacizumabe
- Irinotecano
Outros números de identificação do estudo
- 06-100
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
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