Oxaliplatin and Bortezomib in Treating Patients With Advanced Cancer
A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy
Visão geral do estudo
Status
Descrição detalhada
OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and bortezomib in patients with advanced malignancy.
II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine the toxicity profile of this regimen in these patients. IV. Determine the antitumor activity of this regimen in these patients. V. Determine the pattern of neurotoxicity and its reversibility in patients responding to prolonged administration of this treatment regimen.
VI. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib are altered by the administration of the other agent in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the maximum tolerated doses (MTDs) are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed for at least 3 months.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-15 months.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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New York
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Bronx, New York, Estados Unidos, 10467-2490
- Montefiore Medical Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
Histologically confirmed malignancy for which standard curative or palliative measures do not exist or are no longer effective
- Metastatic or unresectable disease
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100
- More than 6 months
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- AST and ALT no greater than 5 times upper limit of normal
- Creatinine no greater than 1.5 mg/dL
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to any platinum or other study agents
- No pre-existing peripheral neuropathy
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other concurrent uncontrolled illness
- Prior thalidomide allowed provided patient has no clinical neuropathy
- Prior platinum or antitubulin agents allowed provided patient has no clinical neuropathy
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
- More than 3 weeks since prior radiotherapy and recovered
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational or commercial agents or therapies for the malignancy
Plano de estudo
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: Treatment (oxaliplatin, bortezomib)
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the MTDs are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. |
Estudos correlativos
Dado IV
Outros nomes:
Estudos correlativos
Outros nomes:
Dado IV
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Probability of dose escalation according to true dose limiting toxicity (DLT) rate, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
Prazo: Up to 28 days
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Up to 28 days
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Area under the curve (AUC) estimates
Prazo: Days 1 and 15 (course 1)
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Nonlinear compartmental analysis of the oxaliplatin pharmacokinetic data will be performed.
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Days 1 and 15 (course 1)
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Pharmacodynamic assessments (20S proteasome inhibition data)
Prazo: Days 1 and 15 (course 1)
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Summarized by dose and time using standard descriptive statistics.
Asssessments will correlate the AUC in an Emax inhibitory model.
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Days 1 and 15 (course 1)
|
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Sequence of drug administration in terms of PK interaction
Prazo: Days 1 and 15 (course 1)
|
AUC for oxaliplatin and 20-S proteasome inhibition will be calculated and compared for intra-patient variation using paired T-test.
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Days 1 and 15 (course 1)
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Howard Hochster, Montefiore Medical Center
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
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- NCI-2012-02552
- N01CM62204 (Concessão/Contrato do NIH dos EUA)
- NYU 02-12
- CDR0000316444 (Identificador de registro: PDQ (Physician Data Query))
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