Circulating Tumor Cells and Tumor DNA in HCC and NET
27 de abril de 2021 atualizado por: University of Aarhus
Circulating Tumor Cells and Tumor DNA in HCC and NET - Patient-specific Biomarkers for Clinical Decision Support and Tailored Relapse Diagnostics
Background Treatment and control of cancer is associated with high costs, to patients in the form of side effects and discomfort during investigations, to society in the form of expensive drugs and studies.
Circulating tumor cells (CTC) has received great attention as a cancer biomarker in trying to estimate future course in patients with breast cancer, colon cancer and prostate cancer. CTC is believed to be a crucial step in cancer spreading to the bloodstream and giving rise to metastases. Detection of circulating tumor DNA (ctDNA) specifically adds specificity to the analysis of the CTC.
The investigators would like to with molecular biological methods predict which patients requires special monitoring and individualized therapy and explore these tests as clinical decision support.
Purpose and method
In a blood sample from patients with neuro-endocrine tumor (NET) and hepatocellular carcinoma (HCC), the investigators will by cell separation, flow cytometry and DNA sequencing and digital polymerase chain reaction (PCR):
- Identify and isolate the CTC and investigate these for tumor-specific mutations.
- Quantify ctDNA and analyze this for specific mutations, which in the past has been found frequent in NET and HCC.
- Compare findings of mutations on CTC and ctDNA with mutations in tissue biopsies.
The results are compared with the clinical data on disease course, including the effect of treatment and survival.
Subjects 40 Patients with small intestinal/unknown primary NET before treatment with somatostatin analogues 30 patients with pancreatic NET before treatment with Everolimus 30 patients with presumed radically treated HCC 30 patients with HCC in treatment with Sorafenib A blood sample will be taken prior to the start of treatment, after 1 month after start of treatment and thereafter every 3.-6. month for up to two years.
Perspectives In several cancer types molecular diagnostics have had significant influence in treatment and control strategy. The goal is in future to be able to take advantage of a so-called "liquid biopsy" as clinical decision support. The study will bring new knowledge to this growing field of research.
Visão geral do estudo
Status
Concluído
Tipo de estudo
Observacional
Inscrição (Real)
167
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
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Aarhus C
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Aarhus, Aarhus C, Dinamarca, 8000
- Department of Hepatology and Gastroenterology
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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 Não Probabilística
População do estudo
40 patients newly diagnosed NET patients referred for somatostatin analogue treatment for small intestinal NET or NET with unknown primary.
30 Pancreatic NET patients treated for known residual disease will be monitored for possible progression of disease and response to Everolimus 30 HCC patients supposed radically treated, either by RFA or liver resection, will be followed with regard to relapse.
30 HCC patients treated with Sorafenib monitored for treatment response
Descrição
Inclusion Criteria:
- one of the above mentioned diseases
- planed surgery, RFA, Somatostatin Analogue, Sorafenib or Everolimus treatment
- signed informed consent
Exclusion Criteria:
- age below 18, concomitant invasive cancer (not skin cancer) and planed emigration of Denmark.
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
- Modelos de observação: Coorte
- Perspectivas de Tempo: Prospectivo
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
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HCC sorafenib
HCC patients referred for Sorafenib treatment
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Outros nomes:
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HCC curative treatment
HCC patient undergoing potential curative treatment, eg.
radiofrequency ablation (RFA) or resection
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Intended curative surgery or RFA
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NET everolimus
Pancreatic NET patients referred for Everolimus treatment
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Outros nomes:
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NET ssta
Small intestinal or unknown primary NET patients referred for treatment with somatostatin analogues, eg.
lanreotide and octreotide
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Or other somatostatin analogues (SSTA), eg.
Sandostatin
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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Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA
Prazo: 2 months
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Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies
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2 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)
Prazo: 3 years
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3 years
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Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and treatment response according to RECIST criteria
Prazo: up to 5 years
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Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
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up to 5 years
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Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival
Prazo: up to 5 years
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Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
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up to 5 years
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Correlations between mutations fund in circulating DNA and circulating tumor cells
Prazo: 3 years
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Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
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3 years
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Investigadores
- Cadeira de estudo: Jens Kelsen, Consultant, Department of Hepatology and Gastroenterology, Aarhus University Hospital
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2. doi: 10.1002/hep.24199. No abstract available.
- Janson ET, Sorbye H, Welin S, Federspiel B, Gronbaek H, Hellman P, Ladekarl M, Langer SW, Mortensen J, Schalin-Jantti C, Sundin A, Sundlov A, Thiis-Evensen E, Knigge U. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. Acta Oncol. 2014 Oct;53(10):1284-97. doi: 10.3109/0284186X.2014.941999. Epub 2014 Aug 20.
- Zhang Y, Li J, Cao L, Xu W, Yin Z. Circulating tumor cells in hepatocellular carcinoma: detection techniques, clinical implications, and future perspectives. Semin Oncol. 2012 Aug;39(4):449-60. doi: 10.1053/j.seminoncol.2012.05.012.
- Khan MS, Tsigani T, Rashid M, Rabouhans JS, Yu D, Luong TV, Caplin M, Meyer T. Circulating tumor cells and EpCAM expression in neuroendocrine tumors. Clin Cancer Res. 2011 Jan 15;17(2):337-45. doi: 10.1158/1078-0432.CCR-10-1776. Epub 2011 Jan 11.
- Khan MS, Kirkwood A, Tsigani T, Garcia-Hernandez J, Hartley JA, Caplin ME, Meyer T. Circulating tumor cells as prognostic markers in neuroendocrine tumors. J Clin Oncol. 2013 Jan 20;31(3):365-72. doi: 10.1200/JCO.2012.44.2905. Epub 2012 Dec 17.
- Schulze K, Gasch C, Staufer K, Nashan B, Lohse AW, Pantel K, Riethdorf S, Wege H. Presence of EpCAM-positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma. Int J Cancer. 2013 Nov;133(9):2165-71. doi: 10.1002/ijc.28230. Epub 2013 Jun 11.
- Guo W, Yang XR, Sun YF, Shen MN, Ma XL, Wu J, Zhang CY, Zhou Y, Xu Y, Hu B, Zhang X, Zhou J, Fan J. Clinical significance of EpCAM mRNA-positive circulating tumor cells in hepatocellular carcinoma by an optimized negative enrichment and qRT-PCR-based platform. Clin Cancer Res. 2014 Sep 15;20(18):4794-805. doi: 10.1158/1078-0432.CCR-14-0251. Epub 2014 Jul 9.
- Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, Banck MS, Kanwar R, Kulkarni AA, Karpathakis A, Manzo V, Contractor T, Philips J, Nickerson E, Pho N, Hooshmand SM, Brais LK, Lawrence MS, Pugh T, McKenna A, Sivachenko A, Cibulskis K, Carter SL, Ojesina AI, Freeman S, Jones RT, Voet D, Saksena G, Auclair D, Onofrio R, Shefler E, Sougnez C, Grimsby J, Green L, Lennon N, Meyer T, Caplin M, Chung DC, Beutler AS, Ogino S, Thirlwell C, Shivdasani R, Asa SL, Harris CR, Getz G, Kulke M, Meyerson M. Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet. 2013 Dec;45(12):1483-6. doi: 10.1038/ng.2821. Epub 2013 Nov 3.
- Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA Jr, Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011 Mar 4;331(6021):1199-203. doi: 10.1126/science.1200609. Epub 2011 Jan 20.
- Marinoni I, Kurrer AS, Vassella E, Dettmer M, Rudolph T, Banz V, Hunger F, Pasquinelli S, Speel EJ, Perren A. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology. 2014 Feb;146(2):453-60.e5. doi: 10.1053/j.gastro.2013.10.020. Epub 2013 Oct 19.
- Pipinikas CP, Dibra H, Karpathakis A, Feber A, Novelli M, Oukrif D, Fusai G, Valente R, Caplin M, Meyer T, Teschendorff A, Bell C, Morris TJ, Salomoni P, Luong TV, Davidson B, Beck S, Thirlwell C. Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2015 Jun;22(3):L13-8. doi: 10.1530/ERC-15-0108. Epub 2015 Apr 21. No abstract available.
- Rimassa L, Santoro A. Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial. Expert Rev Anticancer Ther. 2009 Jun;9(6):739-45. doi: 10.1586/era.09.41.
- Schulze K, Imbeaud S, Letouze E, Alexandrov LB, Calderaro J, Rebouissou S, Couchy G, Meiller C, Shinde J, Soysouvanh F, Calatayud AL, Pinyol R, Pelletier L, Balabaud C, Laurent A, Blanc JF, Mazzaferro V, Calvo F, Villanueva A, Nault JC, Bioulac-Sage P, Stratton MR, Llovet JM, Zucman-Rossi J. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015 May;47(5):505-511. doi: 10.1038/ng.3252. Epub 2015 Mar 30.
- Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014 May;20(5):548-54. doi: 10.1038/nm.3519. Epub 2014 Apr 6.
- Sorensen BS, Wu L, Wei W, Tsai J, Weber B, Nexo E, Meldgaard P. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib. Cancer. 2014 Dec 15;120(24):3896-901. doi: 10.1002/cncr.28964. Epub 2014 Aug 7.
- Neychev V, Steinberg SM, Cottle-Delisle C, Merkel R, Nilubol N, Yao J, Meltzer P, Pacak K, Marx S, Kebebew E. Mutation-targeted therapy with sunitinib or everolimus in patients with advanced low-grade or intermediate-grade neuroendocrine tumours of the gastrointestinal tract and pancreas with or without cytoreductive surgery: protocol for a phase II clinical trial. BMJ Open. 2015 May 19;5(5):e008248. doi: 10.1136/bmjopen-2015-008248.
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 novembro de 2016
Conclusão Primária (Real)
8 de janeiro de 2020
Conclusão do estudo (Real)
8 de janeiro de 2020
Datas de inscrição no estudo
Enviado pela primeira vez
18 de novembro de 2016
Enviado pela primeira vez que atendeu aos critérios de CQ
21 de novembro de 2016
Primeira postagem (Estimativa)
25 de novembro de 2016
Atualizações de registro de estudo
Última Atualização Postada (Real)
28 de abril de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
27 de abril de 2021
Última verificação
1 de novembro de 2016
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do aparelho digestivo
- Processos Patológicos
- Neoplasias por Tipo Histológico
- Neoplasias
- Neoplasias por local
- Adenocarcinoma
- Carcinoma
- Neoplasias Glandulares e Epiteliais
- Neoplasias do Aparelho Digestivo
- Doenças do Fígado
- Tumores Neuroectodérmicos
- Neoplasias, Células Germinativas e Embrionárias
- Neoplasias, Tecido Nervoso
- Neoplasias Hepáticas
- Processos Neoplásicos
- Neoplasia Metástase
- Carcinoma Hepatocelular
- Tumores Neuroendócrinos
- Células Neoplásicas Circulantes
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes gastrointestinais
- Agentes Antineoplásicos Hormonais
- Inibidores de proteína quinase
- Sorafenibe
- Octreotida
- Everolimo
- Lanreotida
Outros números de identificação do estudo
- SK-HCC-NET
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Não
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 .
Ensaios clínicos em Everolimo
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Seung-Jung ParkAbbott Medical Devices; CardioVascular Research Foundation, KoreaRescindidoDoença arterial coronáriaTailândia, Republica da Coréia, China, Malásia