Circulating Tumor Cells and Tumor DNA in HCC and NET
27. april 2021 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Observationel
Tilmelding (Faktiske)
167
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Aarhus C
-
Aarhus, Aarhus C, Danmark, 8000
- Department of Hepatology and Gastroenterology
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
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
Beskrivelse
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.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: Kohorte
- Tidsperspektiver: Fremadrettet
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
|
HCC sorafenib
HCC patients referred for Sorafenib treatment
|
Andre navne:
|
|
HCC curative treatment
HCC patient undergoing potential curative treatment, eg.
radiofrequency ablation (RFA) or resection
|
Intended curative surgery or RFA
|
|
NET everolimus
Pancreatic NET patients referred for Everolimus treatment
|
Andre navne:
|
|
NET ssta
Small intestinal or unknown primary NET patients referred for treatment with somatostatin analogues, eg.
lanreotide and octreotide
|
Or other somatostatin analogues (SSTA), eg.
Sandostatin
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA
Tidsramme: 2 months
|
Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies
|
2 months
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)
Tidsramme: 3 years
|
3 years
|
|
|
Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and treatment response according to RECIST criteria
Tidsramme: up to 5 years
|
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
|
up to 5 years
|
|
Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival
Tidsramme: up to 5 years
|
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
|
up to 5 years
|
|
Correlations between mutations fund in circulating DNA and circulating tumor cells
Tidsramme: 3 years
|
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
|
3 years
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Jens Kelsen, Consultant, Department of Hepatology and Gastroenterology, Aarhus University Hospital
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. november 2016
Primær færdiggørelse (Faktiske)
8. januar 2020
Studieafslutning (Faktiske)
8. januar 2020
Datoer for studieregistrering
Først indsendt
18. november 2016
Først indsendt, der opfyldte QC-kriterier
21. november 2016
Først opslået (Skøn)
25. november 2016
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
28. april 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
27. april 2021
Sidst verificeret
1. november 2016
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Patologiske processer
- Neoplasmer efter histologisk type
- Neoplasmer
- Neoplasmer efter sted
- Adenocarcinom
- Karcinom
- Neoplasmer, kirtel og epitel
- Neoplasmer i fordøjelsessystemet
- Leversygdomme
- Neuroektodermale tumorer
- Neoplasmer, kimceller og embryonale
- Neoplasmer, nervevæv
- Neoplasmer i leveren
- Neoplastiske processer
- Neoplasma Metastase
- Carcinom, hepatocellulært
- Neuroendokrine tumorer
- Neoplastiske celler, cirkulerende
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Gastrointestinale midler
- Antineoplastiske midler, hormonelle
- Proteinkinasehæmmere
- Sorafenib
- Octreotid
- Everolimus
- Lanreotid
Andre undersøgelses-id-numre
- SK-HCC-NET
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .