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Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer

15 de dezembro de 2015 atualizado por: Memorial Sloan Kettering Cancer Center

A Phase I/II Trial to Assess the Tolerability of RAD 001 With Gefitinib in Patients With Glioblastoma Multiforme and Prostate Cancer and Efficacy in Patients With Castrate Metastatic Prostate Cancer

RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining everolimus with gefitinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with gefitinib and to see how well they work in treating patients with progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to accrual 10/19/06).

Visão geral do estudo

Descrição detalhada

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of everolimus when given in combination with gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I)
  • Determine the safety and efficacy of this regimen in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to accrual as of 10/19/2006). (Phase II)

Secondary

  • Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib in patients treated with this regimen.
  • Determine the association between clinical outcomes and markers that may predict sensitivity of a tumor in patients treated with this regimen.
  • Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens and peripheral blood mononuclear cells from these patients.

OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus followed by a phase II study.

  • Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus 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 (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Tipo de estudo

Intervencional

Inscrição (Real)

61

Estágio

  • Fase 2
  • Fase 1

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

      • Barcelona, Espanha, 08035
        • Vall d'Hebron University Hospital
    • New York
      • New York, New York, Estados Unidos, 10065
        • Memorial Sloan Kettering Cancer Center

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 a 120 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Macho

Descrição

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Glioblastoma multiforme (GBM) (phase I only)

      • Progressive disease despite standard therapy
      • Progressive disease based on 1 of the following:

        • New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
        • New or prior lesions that have increased in size by physical examination
      • Patients who had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true disease progression (rather than radiation necrosis) by positron-emission tomography scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation
    • Castrate metastatic prostate cancer (closed to accrual as of 10/19/2006) (phase I and II)

      • Progressive disease despite standard therapy AND castrate levels < 50 ng/dL of testosterone
      • Progressive disease based on 1 or more of the following:

        • A minimum of 3 rising levels of prostate-specific antigen (PSA) that are obtained 1 or more weeks apart OR 2 rising PSA values obtained more than 1 month apart with at least a 25% increase over the range of values
        • New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
        • New metastatic lesions
      • Patients on an antiandrogen as part of initial therapy must show disease progression after discontinuation of the antiandrogen
      • Patients who have not undergone surgical orchiectomy must continue with medical therapy (e.g., gonadotropin-releasing hormone analogs) to maintain castrate levels of serum testosterone
  • No brain metastases

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3

Hepatic

  • ALT and AST ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 mg/dL

Renal

  • Creatinine within 1.5 times ULN (< 1.95 mg/dL at MSKCC)

Cardiovascular

  • No significant cardiovascular disease
  • No congestive heart failure
  • No New York Heart Association class III or IV cardiac disease
  • No active angina pectoris
  • No myocardial infarction within the past 6 months

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious medical illness
  • No severe infection
  • No severe malnutrition
  • No other active malignancy except non-melanoma skin cancer

    • Patients are not considered to have an active malignancy if they have completed prior therapy and currently have a < 30% risk for relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent biological therapy
  • No concurrent immunotherapy

Chemotherapy

  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • Prior recent resection of recurrent or progressive GBM allowed provided patient has recovered
  • More than 4 weeks since prior major surgery

Other

  • Recovered from all prior therapy
  • More than 4 weeks since prior investigational anticancer drugs
  • No concurrent anticonvulsant that interacts with CYP3A4 (e.g., phenytoin, carbamazepine, or phenobarbital)
  • No other concurrent cytotoxic therapy
  • No other concurrent investigational or commercial agents or therapies for the malignancy

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
Experimental: Everolimus (RAD-001) and Gefitinib

•Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus 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 (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Overall Objective Response
Prazo: 2 years
Response will be evaluated in this study using the new international criteria Response Evaluation Criteria in Solid Tumors (RECIST)
2 years

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Investigadores

  • Investigador principal: Lauren E. Abrey, MD, Memorial Sloan Kettering Cancer Center
  • Investigador principal: Howard I. Scher, MD, Memorial Sloan Kettering Cancer Center
  • Investigador principal: Neal Rosen, MD, Memorial Sloan Kettering Cancer Center

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 março de 2004

Conclusão Primária (Real)

1 de fevereiro de 2008

Conclusão do estudo (Real)

1 de fevereiro de 2008

Datas de inscrição no estudo

Enviado pela primeira vez

10 de junho de 2004

Enviado pela primeira vez que atendeu aos critérios de CQ

10 de junho de 2004

Primeira postagem (Estimativa)

11 de junho de 2004

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

20 de janeiro de 2016

Última atualização enviada que atendeu aos critérios de controle de qualidade

15 de dezembro de 2015

Última verificação

1 de dezembro de 2015

Mais Informações

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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