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Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors

21 de fevereiro de 2014 atualizado por: National Cancer Institute (NCI)

Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates

This phase I trial is studying the side effects of decitabine when given together with or without interferon alfa-2b, and the best dose of interferon alfa-2b, in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as interferon alfa-2b, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether decitabine is more effective when given with or without interferon alfa-2b in treating solid tumors.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Descrição detalhada

PRIMARY OBJECTIVES:

I. To assess toxicities of decitabine plus escalating doses of pegylated interferon alfa-2b (PEG-Intron) in patients with metastatic solid tumor.

II. To identify the dose-limiting toxicity of decitabine in combination with escalating doses of pegylated interferon alfa-2b in these patients.

III. To identify the maximum tolerated dose of pegylated interferon alfa-2b in combination with decitabine in these patients.

SECONDARY OBJECTIVES:

I. To evaluate pretreatment and post-treatment blood and tumor samples to identify changes in global (genomic) DNA methylation.

II. To evaluate pretreatment and post-treatment blood, skin and tumor samples to identify changes in Mage-1 mRNA and protein expression, DNMT-1 levels (due to sequestration by 5-azacytidine), p53 induction (evidence of DNA damage response), as well as changes in levels of 2'5'-oligoadenylate synthesis, MxA and HLA class I as indicators of interferon response.

III. To evaluate complete and partial response rates in patients receiving decitabine in combination with escalating doses of pegylated interferon alfa-2b.

OUTLINE:

This is a dose-escalation study of pegylated interferon alfa-2b. Patients are assigned to 1 of 2 treatment groups.

GROUP 1 (control): Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression after the first course of treatment may crossover to receive treatment in group 2.

GROUP 2: Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample, normal skin, and tissue biopsy collection at baseline and periodically during study. Blood, normal skin, and tissue samples are analyzed for global (genomic) DNA methylation (gene-promoter methylation, gene and protein expression, p53 induction by DNA damage) and interferon levels by high-performance (pressure) liquid chromatography and PCR methylation assays, and for pharmacodynamic studies.

After completion of study treatment, patients are followed at 28 days and then every 3 months.

Tipo de estudo

Intervencional

Inscrição (Real)

30

Estágio

  • 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

  • Estados Unidos
    • Nevada
      • Las Vegas, Nevada, Estados Unidos, 89135
        • Nevada Cancer Institute-Summerlin Campus

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 e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Biopsy-proven solid tumor

    • Metastatic or unresectable disease
  • Tumor amenable to biopsy
  • No curative or more effective treatment for this disease exists, in the opinion of the investigator
  • Measurable disease by scans as assessed by RECIST criteria

  • No untreated brain metastasis

    • No longer receiving steroid therapy for previously treated brain metastasis
  • Zubrod performance status of 0-2
  • Bilirubin ≤ 1.5 times upper limit normal (ULN)
  • SGOT or SGPT ≤ 2.5 times ULN (≤ 5 ULN if hepatic metastases present)
  • Serum creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • ANC > 1,500/μL
  • Platelet count > 100,000/μL
  • Hemoglobin > 9 g/dL (transfusion allowed)
  • No NYHA class III-IV cardiac problems (e.g., congestive heart failure or myocardial infarction within the past 2 months)
  • No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy
  • Willing to undergo biopsies
  • No medical or psychological conditions that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete the treatment, or to grant reliable informed consent
  • No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I, II, or III cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
  • No prior extensive pelvic irradiation or prolonged nucleoside analogue pretreatment
  • At least 28 days since prior and no concurrent chemotherapy, radiotherapy, surgery, biological therapy, anticancer agent, or other investigational drug

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: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador Ativo: Group 1 (chemotherapy)
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients whose disease is not responding after the first course may crossover to group 2.
Outro: análise laboratorial de biomarcadores
Estudos correlativos
Medicamento: decitabina
Dado IV
Outros nomes:
  • DAC
  • 5-aza-dCyd
  • 5AZA
Experimental: Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Outro: análise laboratorial de biomarcadores
Estudos correlativos
Medicamento: decitabina
Dado IV
Outros nomes:
  • DAC
  • 5-aza-dCyd
  • 5AZA
Biológico: peginterferon alfa-2b
Given SC
Outros nomes:
  • interferon alfa-2b peguilado
  • PEG-IFN alfa-2b
  • polietilenoglicol IFN-A2b

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Prazo: Up to 28 days
The type, frequency, and severity of each toxicity will be reported.
Up to 28 days
Dose-limiting toxicity (DLT) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
Prazo: First 28-day course
DLT is defined as grade III drug-related non hematologic and/or grade IV drug-related hematologic toxicity.
First 28-day course
Maximum-tolerated dose (MTD) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
Prazo: First 28-day course
The MTD will be the dose level where not more than 1 case of a specific grade III-IV drug-related toxicity is observed, and either 2+toxicities have been observed at the next highest dose level, or the maximum dose-level of PEG-Intron has been reached.
First 28-day course

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC)
Prazo: Baseline to up to day 1 of course 2
Repeated measures analysis of variance and other linear modeling techniques will be used.
Baseline to up to day 1 of course 2
Changes in expression of methylation-regulated genes in human biological tissues
Prazo: Baseline to up to day 1 of course 2
Repeated measures analysis of variance and other linear modeling techniques will be used.
Baseline to up to day 1 of course 2
Complete and partial response rates
Prazo: Up to 1 year
Up to 1 year

Colaboradores e Investigadores

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

Patrocinador

National Cancer Institute (NCI)

Investigadores

  • Investigador principal: Wolfram Samlowski, Nevada Cancer Institute-Summerlin Campus

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 abril de 2009

Conclusão Primária (Real)

1 de outubro de 2010

Datas de inscrição no estudo

Enviado pela primeira vez

18 de junho de 2008

Enviado pela primeira vez que atendeu aos critérios de CQ

18 de junho de 2008

Primeira postagem (Estimativa)

19 de junho de 2008

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

24 de fevereiro de 2014

Última atualização enviada que atendeu aos critérios de controle de qualidade

21 de fevereiro de 2014

Última verificação

1 de outubro de 2011

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • NCI-2009-00295 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
  • CDR0000597624
  • NVCI-0725
  • NVCI 07-25 (Outro identificador: Nevada Cancer Institute-Summerlin Campus)
  • 8224 (Outro identificador: CTEP)
  • R21CA122270 (Concessão/Contrato do NIH dos EUA)

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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