Clinical trial NCT02973204: Circulating Tumor Cells and Tumor DNA in HCC and NET
Official title: Circulating Tumor Cells and Tumor DNA in HCC and NET - Patient-specific Biomarkers for Clinical Decision Support and Tailored Relapse Diagnostics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Carcinoma, Hepatocellular
Neuroendocrine Tumors
Keywords: tumor DNA
circulating tumor cells
biopsy
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2016-11-25
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA
timeFrame: 2 months
Secondary outcomes:
measure: Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)
timeFrame: 3 years
measure: Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and treatment response according to RECIST criteria
timeFrame: up to 5 years
measure: Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival
timeFrame: up to 5 years
measure: Correlations between mutations fund in circulating DNA and circulating tumor cells
timeFrame: 3 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Hepatology and Gastroenterology
state: Aarhus C
Study officials:
affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital
name: Jens Kelsen, Consultant
role: STUDY_CHAIR
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