Circulating Tumor Cells and Tumor DNA in HCC and NET
27 aprile 2021 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Osservativo
Iscrizione (Effettivo)
167
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Aarhus C
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Aarhus, Aarhus C, Danimarca, 8000
- Department of Hepatology and Gastroenterology
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Metodo di campionamento
Campione non probabilistico
Popolazione di studio
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
Descrizione
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.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: Coorte
- Prospettive temporali: Prospettiva
Coorti e interventi
Gruppo / Coorte |
Intervento / Trattamento |
|---|---|
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HCC sorafenib
HCC patients referred for Sorafenib treatment
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Altri nomi:
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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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Altri nomi:
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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
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
up to 5 years
|
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Correlations between mutations fund in circulating DNA and circulating tumor cells
Lasso di tempo: 3 years
|
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
|
3 years
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Investigatori
- Cattedra di studio: Jens Kelsen, Consultant, Department of Hepatology and Gastroenterology, Aarhus University Hospital
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- 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.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 novembre 2016
Completamento primario (Effettivo)
8 gennaio 2020
Completamento dello studio (Effettivo)
8 gennaio 2020
Date di iscrizione allo studio
Primo inviato
18 novembre 2016
Primo inviato che soddisfa i criteri di controllo qualità
21 novembre 2016
Primo Inserito (Stima)
25 novembre 2016
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
28 aprile 2021
Ultimo aggiornamento inviato che soddisfa i criteri QC
27 aprile 2021
Ultimo verificato
1 novembre 2016
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie dell'apparato digerente
- Processi patologici
- Neoplasie per tipo istologico
- Neoplasie
- Neoplasie per sede
- Adenocarcinoma
- Carcinoma
- Neoplasie, ghiandolari ed epiteliali
- Neoplasie dell'apparato digerente
- Malattie del fegato
- Tumori neuroectodermici
- Neoplasie, cellule germinali ed embrionali
- Neoplasie, tessuto nervoso
- Neoplasie del fegato
- Processi neoplastici
- Metastasi neoplastica
- Carcinoma, epatocellulare
- Tumori neuroendocrini
- Cellule Neoplastiche, Circolanti
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti gastrointestinali
- Agenti antineoplastici, ormonali
- Inibitori della chinasi proteica
- Sorafenib
- Octreotide
- Everolimo
- Lanreotide
Altri numeri di identificazione dello studio
- SK-HCC-NET
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .