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Circulating Tumor Cells and Tumor DNA in HCC and NET

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02973204
Recruitment Status : Recruiting
First Posted : November 25, 2016
Last Update Posted : October 12, 2018
Aarhus University Hospital
Information provided by (Responsible Party):
University of Aarhus

Brief Summary:

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.

Condition or disease Intervention/treatment
Carcinoma, Hepatocellular Neuroendocrine Tumors Drug: Sorafenib Procedure: Radiofrequency ablation (RFA) or surgery Drug: Everolimus Drug: Lanreotide

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 130 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: Circulating Tumor Cells and Tumor DNA in HCC and NET - Patient-specific Biomarkers for Clinical Decision Support and Tailored Relapse Diagnostics
Study Start Date : November 2016
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

Group/Cohort Intervention/treatment
HCC sorafenib
HCC patients referred for Sorafenib treatment
Drug: Sorafenib
Other Names:
  • Nexavar
  • Anatomical Therapeutic Chemical Classification System L01XE05

HCC curative treatment
HCC patient undergoing potential curative treatment, eg. radiofrequency ablation (RFA) or resection
Procedure: Radiofrequency ablation (RFA) or surgery
Intended curative surgery or RFA

NET everolimus
Pancreatic NET patients referred for Everolimus treatment
Drug: Everolimus
Other Names:
  • Certican
  • Afinitor
  • Votubia
  • Anatomical Therapeutic Chemical Classification System L01XE10

NET ssta
Small intestinal or unknown primary NET patients referred for treatment with somatostatin analogues, eg. lanreotide and octreotide
Drug: Lanreotide
Or other somatostatin analogues (SSTA), eg. Sandostatin
Other Names:
  • Ipstyl
  • Sandostatin LAR
  • Octreotide

Primary Outcome Measures :
  1. Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA [ Time Frame: 2 months ]
    Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies

Secondary Outcome Measures :
  1. Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts) [ Time Frame: 3 years ]
  2. 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 ]
    Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples

  3. Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival [ Time Frame: up to 5 years ]
    Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples

  4. Correlations between mutations fund in circulating DNA and circulating tumor cells [ Time Frame: 3 years ]
    Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples

Biospecimen Retention:   Samples With DNA
Blood samples and biopsies when available.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02973204

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Contact: Stine Karlsen, MD +4522793193
Contact: Jens Kelsen, Consultant +4530562682

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Department of Hepatology and Gastroenterology Recruiting
Aarhus, Aarhus C, Denmark, 8000
Contact: Stine Karlsen, MD, Phd Student    +4522793193   
Contact: Jens Kelsen, Consultant, PhD    +4530562682   
Principal Investigator: Stine Karlsen, MD, Phd student         
Sponsors and Collaborators
University of Aarhus
Aarhus University Hospital
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Study Chair: Jens Kelsen, Consultant Department of Hepatology and Gastroenterology, Aarhus University Hospital

Additional Information:


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Responsible Party: University of Aarhus Identifier: NCT02973204    
Other Study ID Numbers: SK-HCC-NET
First Posted: November 25, 2016    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Aarhus:
tumor DNA
circulating tumor cells
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasm Metastasis
Neoplasms, Glandular and Epithelial
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplastic Cells, Circulating
Carcinoma, Hepatocellular
Neoplastic Processes
Pathologic Processes
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents