Circulating Tumor Cells and Tumor DNA in HCC and NET

April 27, 2021 updated by: 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):

  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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

167

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Aarhus C
      • Aarhus, Aarhus C, Denmark, 8000
        • Department of Hepatology and Gastroenterology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

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:
  • Afinitor
  • Certican
  • 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:
  • Sandostatin LAR
  • Octreotide
  • Ipstyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 3 years
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital

Investigators

  • Study Chair: Jens Kelsen, Consultant, Department of Hepatology and Gastroenterology, Aarhus University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Actual)

January 8, 2020

Study Completion (Actual)

January 8, 2020

Study Registration Dates

First Submitted

November 18, 2016

First Submitted That Met QC Criteria

November 21, 2016

First Posted (Estimate)

November 25, 2016

Study Record Updates

Last Update Posted (Actual)

April 28, 2021

Last Update Submitted That Met QC Criteria

April 27, 2021

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SK-HCC-NET

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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