- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00629226
Bortezomib, Cetuximab, and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage IV Head and Neck Cancer
Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Radiation therapy uses high energy x- rays to kill tumor cells. Bortezomib and cetuximab may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with cetuximab, radiation therapy, and cisplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with cetuximab and radiation therapy with or without cisplatin in treating patients with stage IV head and neck cancer.
Visão geral do estudo
Status
Condições
Descrição detalhada
OBJECTIVES:
Primary
- To evaluate the feasibility and toxicity of bortezomib, cetuximab, and radiotherapy with or without cisplatin in patients with stage IV squamous cell carcinoma of the head and neck.
- To identify the maximum tolerated dose of bortezomib for further clinical phase II development.
Secondary
- To evaluate the objective response rate, progression-free survival, and overall survival of patients treated with these regimens.
- To determine the effects of bortezomib and cetuximab with or without cisplatin on inhibiting activation of the NF-kB, EGFR, MAPK, and STAT3 signal pathways, expression of pro-survival and pro-angiogenesis genes regulated by these pathways, and on proliferation, apoptosis, and angiogenesis.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are simultaneously accrued to 1 of 2 treatment groups. Patients are initially accrued to group I until there are a sufficient number of patients to establish the maximum tolerated dose (MTD) of bortezomib. Patients are then accrued to group II.
- Group I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, 11, 22, 25, 29, 32, 43, 46, 50, and 53. Beginning on day 8 or 9, patients undergo standard intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for up to 8 weeks.
Once the MTD of bortezomib is determined, at least 6 and up to 10 additional patients are accrued and treated at the MTD.
- Group II: Patients receive cetuximab, bortezomib (beginning at one dose level below the MTD determined in group I), and IMRT as in group I. Patients also receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.
Once the MTD of bortezomib is determined, 6 additional patients are accrued and treated at the MTD.
Patients undergo blood sample collection periodically for correlative laboratory studies. Samples are analyzed for biomarkers by immunohistochemistry, quantitative reverse transcriptase-polymerase chain reaction, and ELISA.
After completion of study therapy, patients are followed periodically for 2-5 years.
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Fase 1
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 Trials Referral Office
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- UPMC Cancer Centers
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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 squamous cell carcinoma of the head and neck, including variants or undifferentiated/poorly differentiated carcinoma
- Previously untreated stage IV disease OR residual disease or regionally recurrent disease after prior surgery and/or chemotherapy
- Must be eligible to receive full-dose radiotherapy and be evaluated and accepted for treatment by a Radiation Oncologist
- No clinically measurable distant disease OR has asymptomatic small distant lesions outside the radiation field ≤ 3 cm in individual or aggregate diameter for which palliation of local and regional disease is clearly warranted
No previously untreated nasopharyngeal cancer (any stage)
- Recurrent nasopharyngeal carcinoma allowed
- No known brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
- ANC ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin normal (indirect bilirubin ≤ 3 mg/dL in patients with Gilbert's syndrome)
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Adequate cognitive and neurologic function
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, cetuximab, cisplatin, or other agents used in this study
- No peripheral sensory neuropathy ≥ grade 2
No concurrent uncontrolled illness including, but not limited to, the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would preclude study compliance
- HIV-negative
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 3 months since prior cisplatin
- No prior radiotherapy to the head and neck
- No prior systemic EGFR inhibitors
- No prior bortezomib
- No other concurrent investigational agents
- No other concurrent anticancer therapy
- No concurrent antiretroviral therapy
- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
- No concurrent amifostine
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Group I
Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50.
Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, 11, 22, 25, 29, 32, 43, 46, 50, and 53.
Beginning on day 8 or 9, patients undergo standard intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for up to 8 weeks.
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Dado IV
Dado IV
Once daily, 5 days a week, for up to 8 weeks
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Experimental: Group II
Patients receive cetuximab, bortezomib (beginning at one dose level below the MTD determined in group I), and IMRT as in group I. Patients also receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.
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Dado IV
Dado IV
Dado IV
Once daily, 5 days a week, for up to 8 weeks
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
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Dose-limiting toxicities and other toxicities as assessed by NCI CTCAE v3.0
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Maximum tolerated dose of bortezomib when administered in combination with cetuximab and radiotherapy with and without cisplatin
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Medidas de resultados secundários
Medida de resultado |
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Sobrevida livre de progressão
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Sobrevida geral
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Taxa de resposta objetiva
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Pre-to-post-treatment changes in biomarkers
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Carter Van Waes, MD, PhD, National Institute on Deafness and Other Communication Disorders (NIDCD)
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (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
- Carcinoma espinocelular estágio IV de lábio e cavidade oral
- carcinoma epidermóide recorrente de lábio e cavidade oral
- Carcinoma espinocelular estágio IV de orofaringe
- Carcinoma espinocelular recorrente de orofaringe
- carcinoma espinocelular recorrente de nasofaringe
- Carcinoma espinocelular de hipofaringe estágio IV
- carcinoma epidermóide recorrente de hipofaringe
- Carcinoma espinocelular estágio IV da laringe
- carcinoma espinocelular recorrente da laringe
- Carcinoma espinocelular estágio IV de seios paranasais e cavidade nasal
- carcinoma espinocelular recorrente de seios paranasais e cavidade nasal
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 080071, CDR0000588196
- NCI-08-C-0071
- CCR 7205
- NCI-7893
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