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Biomarker Development for Response Prediction by DNA Mutational Analysis (CPCT-01)

7 de março de 2018 atualizado por: P.O. Witteveen

Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions

The purpose of this study is to determine whether it is possible to predict response to chemotherapy in patients with metastatic cancer who are treated with irinotecan by determining the mutational profile of the tumor.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Tipo de estudo

Observacional

Inscrição (Real)

79

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

  • Holanda
      • Utrecht, Holanda, 3584 CX
        • University Medical Center Utrecht
    • North Holland
      • Amsterdam, North Holland, Holanda, 1066 CX
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    • South Holland
      • Rotterdam, South Holland, Holanda, 3075 EA
        • Erasmsus Medical Center - Daniël den Hoed clinic

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

Método de amostragem

Amostra de Probabilidade

População do estudo

Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.

Descrição

Inclusion Criteria:

  1. Patients with a metastatic solid tumor who have failed at least one line of palliative chemotherapy and are irinotecan naïve.
  2. Patients who are, as per local protocol, eligible for palliative treatment with (standard of care) irinotecan.
  3. Measurable metastatic lesion(s), according to RECIST 1.1 criteria.

  4. Radiological measurable metastatic lesion(s) of which a histological biopsy can safely be obtained:

    1. Patients with safely accessible metastases.
    2. Patients not known with bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.
    3. Patients not using any anti-coagulant medication at the time of biopsy: all aspirin derivatives, NSAID's, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors are not allowed, unless medication can either be safely stopped or counteracted.

    4. Adequate coagulation status on the day of biopsy as measured by:

      • PTT < 1.5 x ULN
      • APTT < 1.5 x ULN
      • Platelet count 100 x 10*9 / L or higher
      • PT-INR < 1.6
      • HB > 6
    5. Biopsies should be performed at least four weeks after last bevacizumab administration.
  5. Patients age 18 years or up, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.

Exclusion Criteria:

Patients not meeting all of the above inclusion criteria.

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

Coortes e Intervenções

Grupo / Coorte
Intervenção / Tratamento
Irinotecan

Patients will be subjected to a their metastatic solid tumor. Radiological response will be evaluated after each 2 cycles: 1. percentage change in radiological volume of the "index lesion" (radiological measurable lesion that underwent biopsy) after the first two cycles of irinotecan; 2. radiological response according to RECIST 1.1 after each 2 cycles. Patients are intended to receive irinotecan until progressive disease or unacceptable toxicity. Patients will be subjected to another biopsy of the index lesion at definitive discontinuation of irinotecan. Patients will also be subjected to blood draws for determining patient's genetic background variation.

Side studies include:

  • pharmacogenetics
  • pharmacokinetics of SN-38
  • carboxylesterase activity in the index lesion
  • midazolam clearance test (only in Rotterdam patients)
Procedimento: Biopsy
Histological biopsy of the "index lesion" (a radiological measurable lesion on which biopsy is performed) at baseline, as well as when showing progressive disease. Histological biopsies will be subjected to DNA sequencing to assess the mutational profile, as well as to analysis of carboxylesterase activity.
Outros nomes:
  • Histological biopsy
Procedimento: Blood samples
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
Outros nomes:
  • Amostra de sangue
Procedimento: Pharmacokinetics
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
Outros nomes:
  • PK
  • Pharmacokinetic analysis
  • Pharmacokinetic analyses
Procedimento: Midazolam clearance test
Patients who are being treated in Rotterdam will be subjected to blood draws for validation of the earlier developed midazolam phenotyping test (midazolam clearance test), which may be an indicator for pharmacokinetics of irinotecan.
Outros nomes:
  • MCT

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
Exploration of the correlation between the mutational profile and the percentage change in volumetric measurement of the index lesion after the first two cycles of chemotherapy.
Prazo: Change in radiological volume of the index lesion after the first 2 cycles of irinotecan. Radiological response (according to RECIST 1.1) after the first 2 cycles of irinotecan (i.e. after 2 x 3 weeks = 6 weeks)
Change in radiological volume of the index lesion after the first 2 cycles of irinotecan. Radiological response (according to RECIST 1.1) after the first 2 cycles of irinotecan (i.e. after 2 x 3 weeks = 6 weeks)

Medidas de resultados secundários

Medida de resultado
Prazo
Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
Prazo: Analysis 6 weeks after initiation of treatment
Analysis 6 weeks after initiation of treatment
Exploration of the correlation between the mutational profile and progression free survival and overall survival.
Prazo: Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
Exploration of the correlation between the mutational profile of the index lesion and patient's germline DNA background variation.
Prazo: Analysis after progressive disease, on average after 3 months.
Analysis after progressive disease, on average after 3 months.
Differences in mutational profile of metastasis prior to and after exposure to treatment.
Prazo: Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
Determine reliable and valid strategies for statistical analysis for biomarker discovery
Prazo: 2 years
2 years
Correlate response to pharmacokinetics of SN-38
Prazo: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
Determine carboxylesterase activity in metastatic tumor material (pre- and posttreatment) and correlate intra-tumoral carboxylesterase activity to systemic SN-38 pharmacokinetics and to irinotecan response
Prazo: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
Determine clinical applicability of the midazolam phenotyping probe
Prazo: After first cycle of irinotecan, at three weeks
After first cycle of irinotecan, at three weeks
Number and nature of all (serious) adverse events of study related procedures
Prazo: 14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)

Colaboradores e Investigadores

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

Patrocinador

P.O. Witteveen

Colaboradores

Erasmus Medical Center
The Netherlands Cancer Institute

Investigadores

  • Investigador principal: Marlies Langenberg, MD/PhD, UMC Utrecht
  • Investigador principal: Neeltje Steeghs, MD/PhD, Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
  • Investigador principal: Ron Mathijssen, MD/PhD, Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam

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 maio de 2011

Conclusão Primária (Real)

1 de novembro de 2015

Conclusão do estudo (Real)

1 de agosto de 2016

Datas de inscrição no estudo

Enviado pela primeira vez

1 de agosto de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

13 de maio de 2013

Primeira postagem (Estimativa)

16 de maio de 2013

Atualizações de registro de estudo

Última Atualização Postada (Real)

9 de março de 2018

Última atualização enviada que atendeu aos critérios de controle de qualidade

7 de março de 2018

Última verificação

1 de março de 2018

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • NL35198.041.11

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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