- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00516282
VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma
A Phase I/II Trial of Cloretazine® (VNP40101M) and Temodar® (Temozolomide) for Patients With Malignant Glioma in First Relapse or Progression
RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temozolomide may also stop the growth of tumor cells by blocking blood flow to the tumor.
PURPOSE: This phase I/II trial is studying the side effects and best dose of VNP40101M when given together with temozolomide and to see how well it works in treating patients with progressive or relapsed malignant glioma.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of VNP40101M when administered with temozolomide in patients with progressive or relapsed (first relapse) malignant glioma. (Phase I)
- To record the toxicities of VNP40101M when administered with temozolomide. (Phase I and II)
- To measure the level of AGT expression in peripheral blood monocytes before treatment with temozolomide and just prior to the administration of VNP40101M. (Phase I and II)
- To determine MGMT methylation status as well as other methylation patterns in blood and tissue from patients treated with this regimen and correlate with outcome. (Phase I and II)
- To determine the 6- and 12-month progression-free survival rates of patients treated with this regimen. (Phase II)
- To determine overall survival of patients treated with this regimen. (Phase II)
- To determine the complete and partial response rates in patients treated with this regimen. (Phase II)
- To determine CSF penetration of VNP40101M once the MTD is reached from phase I and correlate with serum/plasma pharmacokinetics. (Phase II)
OUTLINE:
- Phase I: Patients receive oral temozolomide on days 1-7 and VNP40101M IV over 15-30 minutes 2 hours after the last dose of temozolomide on day 7. Treatment repeats every 7 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.
- Phase II: Patients receive oral temozolomide and VNP40101M as in phase I. VNP40101M is given at the MTD determined in phase I.
In both phases, patients complete the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire on day 1 of each course.
Blood is collected for in vitro isolation of mononuclear cells for analysis of O^6 alkylguanine DNA alkyltransferase on days 1 and 7 of course 1. Blood, plasma, CSF, and formalin-fixed paraffin-embedded tissue blocks are collected for gene methylation studies, including MGMT, at baseline and on day 1 of each course.
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, 60611-2998
- Hematology-Oncology Associates of Illinois
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Chicago, Illinois, Estados Unidos, 60611-3013
- Northwestern University
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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:
Inclusion criteria:
Histologically proven malignant glioma including any of the following:
- Glioblastoma multiforme
- Gliosarcoma
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic mixed oligoastrocytoma
- Malignant astrocytoma not otherwise specified
- Unequivocal evidence of tumor recurrence or progression by MRI or CT scan with contrast
- No more than one relapse
Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
- More than 2 weeks from surgery and have recovered from the effects of surgery
- Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study if a treatment failure can be evaluated
Enhanced CT scan/ MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively
- If the 96-hour scan is more than 2 weeks from registration, the scan needs to be repeated
- A baseline scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for 5 or more days otherwise a new baseline MRI/CT is required
- The same type of scan (i.e., MRI or CT scan) must be used throughout the period of protocol treatment for tumor measurement
- Must have failed prior external-beam radiotherapy
- Must have failed one prior systemic treatment with chemotherapy or biologic agents
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status 60-100%
- Life expectancy > 12 weeks
- WBC > 3,000/mm³
- ANC > 1,500/mm³
- Platelet count > 100,000/mm³
- Hemoglobin > 10 mg/dL
- AST and ALT < 4 times upper limit of normal (ULN)
- Bilirubin < 2 times ULN
- Creatinine < 1.5 times ULN
- Fertile patients must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device)
- Negative pregnancy test
- Not pregnant or nursing
Exclusion criteria:
- Active uncontrolled bleeding
- Active infection of any kind
- Unwilling or unable to follow protocol requirements or to give informed consent
Active heart disease including any of the following:
- Myocardial infarction within the past 3 months
- Uncontrolled arrhythmias
- Uncontrolled coronary artery disease
- Uncontrolled congestive heart failure
- Known HIV-positive patients (HIV testing is not required)
- History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for that disease for a minimum of 3 years
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- See Disease Characteristics
- Recovered from prior therapy
- At least 2 weeks since prior vincristine
- More than 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas)
- More than 4 weeks since prior radiotherapy
- More than 4 weeks since prior experimental biologic agents (e.g., EGFR inhibitors, etc)
- More than 3 weeks since prior procarbazine administration
More than 2 weeks since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin)
- Radiosensitizer does not count
At least 2 weeks since prior and no concurrent enzyme inducing anticonvulsants
- If patient is on an enzyme inducing anticonvulsant, they may be converted to a non-enzyme inducing anticonvulsant
Exclusion criteria:
- Any other concurrent standard or investigational treatment for cancer, or any other investigational agent for any indication
- Concurrent disulfiram
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)
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
MTD of CLORETAZINE
Prazo: At the end of phase one
|
To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse
|
At the end of phase one
|
Progression-free survival rate
Prazo: End of Phase II
|
To determine the 6 and 12 month progression-free survival rate.
|
End of Phase II
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Toxicities of CLORETAZINE when administered with Temodar®.
Prazo: Adverse events are monitored at screening/baseline;day one; termination visit; followup until death.
|
To record the toxicities of CLORETAZINE when administered with Temodar®. (Toxicity is assessed continuously through routine medical monitoring of the patient throughout each cycle and all adverse events are recorded cumulatively on the case report forms). |
Adverse events are monitored at screening/baseline;day one; termination visit; followup until death.
|
MGMT Methylation Status
Prazo: Baseline and day seven of every cycle
|
To determine MGMT methylation status as well as other methylation patterns in blood correlate with outcome.
|
Baseline and day seven of every cycle
|
Determine overall survival
Prazo: All patients will be followed until death
|
To determine overall survival.
|
All patients will be followed until death
|
Response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse
Prazo: Day one of every cycle
|
To determine the response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse.
|
Day one of every cycle
|
Record the toxicities of CLORETAZINE when administered after Temodar
Prazo: Continuously after the first dose;within thirty days of each administration of investigational agent
|
To record the toxicities of CLORETAZINE when administered after Temodar®
|
Continuously after the first dose;within thirty days of each administration of investigational agent
|
Measure the level of AGT expression
Prazo: Day seven of every cycle
|
To measure the level of AGT expression in peripheral blood monocytes before treatment with Temodar® and just prior to the administration of CLORETAZINE.
|
Day seven of every cycle
|
CSF penetration of CLORETAZINE
Prazo: Day seven of cycle one of Phase 2 only
|
To determine CSF penetration of CLORETAZINE once the MTD is reached from phase I and correlate with serum/plasma PK
|
Day seven of cycle one of Phase 2 only
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
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 Sistema Nervoso
- Neoplasias por Tipo Histológico
- Neoplasias
- Neoplasias por local
- Neoplasias Glandulares e Epiteliais
- Neoplasias Neuroepiteliais
- Tumores Neuroectodérmicos
- Neoplasias, Células Germinativas e Embrionárias
- Neoplasias, Tecido Nervoso
- Glioma
- Neoplasias do Sistema Nervoso
- Neoplasias do Sistema Nervoso Central
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Antineoplásicos
- Agentes Antineoplásicos Alquilantes
- Agentes Alquilantes
- Temozolomida
Outros números de identificação do estudo
- NU 07C1
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