Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.
III. Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.
IV. Determine the safety and toxicity of this regimen in these patients.
SECONDARY OBJECTIVES:
I. Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.
II. Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.
OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.
Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Course 2: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive high-dose ifosfamide as in course 1.
Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.
Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover. In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Illinois
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Chicago, Illinois, Estados Unidos, 60637-1470
- University of Chicago Comprehensive Cancer 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 solid tumor
- Unresectable, metastatic disease
- No primary tumors
- Eligible for high-dose ifosfamide-based therapy
- No known brain metastases
- Performance status - ECOG 0-1
- Performance status - Karnofsky 70-100%
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin normal
- Creatinine normal
- Creatinine clearance ≥ 60 mL/min
- 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 during and for 4 weeks after study participation
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
- No concurrent uncontrolled illness
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
- More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
- No prior hematopoietic stem cell transplantation
- No concurrent pegfilgrastim
- No concurrent immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- No other concurrent chemotherapy
- No concurrent hormonal therapy
- More than 4 weeks since prior radiotherapy and recovered
- No concurrent therapeutic radiotherapy
- More than 4 weeks since prior anticancer therapy
- No more than 2 prior cytotoxic regimens
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer agents or therapies
- No other concurrent investigational agents
Plano de estudo
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 |
|---|---|
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Experimental: Arm I (ifosfamide)
Patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
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Dado IV
Outros nomes:
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Experimental: Arm II (O6-benzylguanine, ifosfamide)
Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
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Dado IV
Outros nomes:
Dado IV
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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Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
Prazo: Baseline up to 1 year
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Baseline up to 1 year
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Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity
Prazo: 21 days
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DLT is defined as any >= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.
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21 days
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Pharmacodynamics including apoptosis and DNA damage
Prazo: Up to 1 year
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Up to 1 year
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Pharmacokinetics of O6-benzylguanine
Prazo: Up to day 3 of course 2
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Summarized using descriptive statistics (mean, median, standard deviation, and interquartile range).
Estimated via nonlinear regression.
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Up to day 3 of course 2
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Sonali Smith, University of Chicago Comprehensive Cancer 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-2012-02601
- U01CA069852 (Concessão/Contrato do NIH dos EUA)
- 12999B
- CDR0000371909 (Identificador de registro: PDQ (Physician Data Query))
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