<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02973204</url>
  </required_header>
  <id_info>
    <org_study_id>SK-HCC-NET</org_study_id>
    <nct_id>NCT02973204</nct_id>
  </id_info>
  <brief_title>Circulating Tumor Cells and Tumor DNA in HCC and NET</brief_title>
  <official_title>Circulating Tumor Cells and Tumor DNA in HCC and NET - Patient-specific Biomarkers for Clinical Decision Support and Tailored Relapse Diagnostics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background Treatment and control of cancer is associated with high costs, to patients in the&#xD;
      form of side effects and discomfort during investigations, to society in the form of&#xD;
      expensive drugs and studies.&#xD;
&#xD;
      Circulating tumor cells (CTC) has received great attention as a cancer biomarker in trying to&#xD;
      estimate future course in patients with breast cancer, colon cancer and prostate cancer. CTC&#xD;
      is believed to be a crucial step in cancer spreading to the bloodstream and giving rise to&#xD;
      metastases. Detection of circulating tumor DNA (ctDNA) specifically adds specificity to the&#xD;
      analysis of the CTC.&#xD;
&#xD;
      The investigators would like to with molecular biological methods predict which patients&#xD;
      requires special monitoring and individualized therapy and explore these tests as clinical&#xD;
      decision support.&#xD;
&#xD;
      Purpose and method&#xD;
&#xD;
      In a blood sample from patients with neuro-endocrine tumor (NET) and hepatocellular carcinoma&#xD;
      (HCC), the investigators will by cell separation, flow cytometry and DNA sequencing and&#xD;
      digital polymerase chain reaction (PCR):&#xD;
&#xD;
        1. Identify and isolate the CTC and investigate these for tumor-specific mutations.&#xD;
&#xD;
        2. Quantify ctDNA and analyze this for specific mutations, which in the past has been found&#xD;
           frequent in NET and HCC.&#xD;
&#xD;
        3. Compare findings of mutations on CTC and ctDNA with mutations in tissue biopsies.&#xD;
&#xD;
      The results are compared with the clinical data on disease course, including the effect of&#xD;
      treatment and survival.&#xD;
&#xD;
      Subjects 40 Patients with small intestinal/unknown primary NET before treatment with&#xD;
      somatostatin analogues 30 patients with pancreatic NET before treatment with Everolimus 30&#xD;
      patients with presumed radically treated HCC 30 patients with HCC in treatment with Sorafenib&#xD;
      A blood sample will be taken prior to the start of treatment, after 1 month after start of&#xD;
      treatment and thereafter every 3.-6. month for up to two years.&#xD;
&#xD;
      Perspectives In several cancer types molecular diagnostics have had significant influence in&#xD;
      treatment and control strategy. The goal is in future to be able to take advantage of a&#xD;
      so-called &quot;liquid biopsy&quot; as clinical decision support. The study will bring new knowledge to&#xD;
      this growing field of research.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">January 8, 2020</completion_date>
  <primary_completion_date type="Actual">January 8, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA</measure>
    <time_frame>2 months</time_frame>
    <description>Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and treatment response according to RECIST criteria</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations between mutations fund in circulating DNA and circulating tumor cells</measure>
    <time_frame>3 years</time_frame>
    <description>Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">167</enrollment>
  <condition>Carcinoma, Hepatocellular</condition>
  <condition>Neuroendocrine Tumors</condition>
  <arm_group>
    <arm_group_label>HCC sorafenib</arm_group_label>
    <description>HCC patients referred for Sorafenib treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCC curative treatment</arm_group_label>
    <description>HCC patient undergoing potential curative treatment, eg. radiofrequency ablation (RFA) or resection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NET everolimus</arm_group_label>
    <description>Pancreatic NET patients referred for Everolimus treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NET ssta</arm_group_label>
    <description>Small intestinal or unknown primary NET patients referred for treatment with somatostatin analogues, eg. lanreotide and octreotide</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <arm_group_label>HCC sorafenib</arm_group_label>
    <other_name>Nexavar</other_name>
    <other_name>Anatomical Therapeutic Chemical Classification System L01XE05</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radiofrequency ablation (RFA) or surgery</intervention_name>
    <description>Intended curative surgery or RFA</description>
    <arm_group_label>HCC curative treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <arm_group_label>NET everolimus</arm_group_label>
    <other_name>Certican</other_name>
    <other_name>Afinitor</other_name>
    <other_name>Votubia</other_name>
    <other_name>Anatomical Therapeutic Chemical Classification System L01XE10</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lanreotide</intervention_name>
    <description>Or other somatostatin analogues (SSTA), eg. Sandostatin</description>
    <arm_group_label>NET ssta</arm_group_label>
    <other_name>Ipstyl</other_name>
    <other_name>Sandostatin LAR</other_name>
    <other_name>Octreotide</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples and biopsies when available.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        40 patients newly diagnosed NET patients referred for somatostatin analogue treatment for&#xD;
        small intestinal NET or NET with unknown primary.&#xD;
&#xD;
        30 Pancreatic NET patients treated for known residual disease will be monitored for&#xD;
        possible progression of disease and response to Everolimus 30 HCC patients supposed&#xD;
        radically treated, either by RFA or liver resection, will be followed with regard to&#xD;
        relapse.&#xD;
&#xD;
        30 HCC patients treated with Sorafenib monitored for treatment response&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  one of the above mentioned diseases&#xD;
&#xD;
          -  planed surgery, RFA, Somatostatin Analogue, Sorafenib or Everolimus treatment&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age below 18, concomitant invasive cancer (not skin cancer) and planed emigration of&#xD;
             Denmark.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jens Kelsen, Consultant</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Hepatology and Gastroenterology, Aarhus University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Hepatology and Gastroenterology</name>
      <address>
        <city>Aarhus</city>
        <state>Aarhus C</state>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>25140861</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21374666</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>22846862</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21224371</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23248251</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23616258</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25009297</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24185511</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21252315</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24148618</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25900181</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>19496710</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25822088</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24705333</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25103305</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25991462</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tumor DNA</keyword>
  <keyword>circulating tumor cells</keyword>
  <keyword>biopsy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Neoplastic Cells, Circulating</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Sorafenib</mesh_term>
    <mesh_term>Octreotide</mesh_term>
    <mesh_term>Lanreotide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02973204
org study id: SK-HCC-NET
nct id: NCT02973204
lead sponsor: 
collaborator: 
has dmc: No
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):

        1. Identify and isolate the CTC and investigate these for tumor-specific mutations.

        2. Quantify ctDNA and analyze this for specific mutations, which in the past has been found
           frequent in NET and HCC.

        3. 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.
observational model: Cohort
time perspective: Prospective
measure: Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA
time frame: 2 months
description: Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies
measure: Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)
time frame: 3 years
measure: Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and treatment response according to RECIST criteria
time frame: up to 5 years
description: Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
measure: Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival
time frame: up to 5 years
description: Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
measure: Correlations between mutations fund in circulating DNA and circulating tumor cells
time frame: 3 years
description: Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
arm group label: HCC sorafenib
description: HCC patients referred for Sorafenib treatment
arm group label: HCC curative treatment
description: HCC patient undergoing potential curative treatment, eg. radiofrequency ablation (RFA) or resection
arm group label: NET everolimus
description: Pancreatic NET patients referred for Everolimus treatment
arm group label: NET ssta
description: Small intestinal or unknown primary NET patients referred for treatment with somatostatin analogues, eg. lanreotide and octreotide
intervention type: Drug
intervention name: Sorafenib
arm group label: HCC sorafenib
other name: Nexavar
other name: Anatomical Therapeutic Chemical Classification System L01XE05
intervention type: Procedure
intervention name: Radiofrequency ablation (RFA) or surgery
description: Intended curative surgery or RFA
arm group label: HCC curative treatment
intervention type: Drug
intervention name: Everolimus
arm group label: NET everolimus
other name: Certican
other name: Afinitor
other name: Votubia
other name: Anatomical Therapeutic Chemical Classification System L01XE10
intervention type: Drug
intervention name: Lanreotide
description: Or other somatostatin analogues (SSTA), eg. Sandostatin
arm group label: NET ssta
other name: Ipstyl
other name: Sandostatin LAR
other name: Octreotide
Blood samples and biopsies when available.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jens Kelsen, Consultant
role: Study Chair
affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital
facility: 
country: Denmark
citation: 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.
PMID: 25140861
citation: 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.
PMID: 21374666
citation: 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.
PMID: 22846862
citation: 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.
PMID: 21224371
citation: 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.
PMID: 23248251
citation: 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.
PMID: 23616258
citation: 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.
PMID: 25009297
citation: 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.
PMID: 24185511
citation: 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.
PMID: 21252315
citation: 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.
PMID: 24148618
citation: 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.
PMID: 25900181
citation: 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.
PMID: 19496710
citation: 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.
PMID: 25822088
citation: 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.
PMID: 24705333
citation: 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.
PMID: 25103305
citation: 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.
PMID: 25991462
responsible party type: Sponsor
mesh term: Neuroendocrine Tumors
mesh term: Neoplastic Cells, Circulating
mesh term: Carcinoma, Hepatocellular
mesh term: Everolimus
mesh term: Sorafenib
mesh term: Octreotide
mesh term: Lanreotide
sharing ipd: No