Circulating Tumor Cells and Tumor DNA in HCC and NET

NCT02973204 | Completed

• 1 other identifier: SK-HCC-NET
• Study Type: observational
• Target: 167
• Locations: 1 country
• Sites: 1

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. 1.Identify and isolate the CTC and investigate these for tumor-specific mutations.
2. 2.Quantify ctDNA and analyze this for specific mutations, which in the past has been found frequent in NET and HCC.
3. 3.Compare findings of mutations on CTC and ctDNA with mutations in tissue biopsies.

Conditions

Carcinoma, Hepatocellular; Neuroendocrine Tumors

Keywords

tumor DNA; circulating tumor cells; biopsy

Outcome Measures

Primary Outcomes (1)

• Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA

  Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies

  2 months

Secondary Outcomes (4)

• Flow cytometry for detection and quantification of CTC in peripheral blood (absolute and relative counts)

  3 years

• Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and treatment response according to RECIST criteria

  up to 5 years

• Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival

  up to 5 years

• Correlations between mutations fund in circulating DNA and circulating tumor cells

  3 years

Study Arms (4)

HCC sorafenib

HCC patients referred for Sorafenib treatment

Drug: Sorafenib

HCC curative treatment

HCC patient undergoing potential curative treatment, eg. radiofrequency ablation (RFA) or resection

Procedure: Radiofrequency ablation (RFA) or surgery

NET everolimus

Pancreatic NET patients referred for Everolimus treatment

Drug: Everolimus

NET ssta

Small intestinal or unknown primary NET patients referred for treatment with somatostatin analogues, eg. lanreotide and octreotide

Drug: Lanreotide

Interventions

Sorafenib DRUG

Also known as: Nexavar, Anatomical Therapeutic Chemical Classification System L01XE05

HCC sorafenib

Radiofrequency ablation (RFA) or surgery PROCEDURE

Intended curative surgery or RFA

HCC curative treatment

Everolimus DRUG

Also known as: Certican, Afinitor, Votubia, Anatomical Therapeutic Chemical Classification System L01XE10

NET everolimus

Lanreotide DRUG

Or other somatostatin analogues (SSTA), eg. Sandostatin

Also known as: Ipstyl, Sandostatin LAR, Octreotide

NET ssta

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• one of the above mentioned diseases
• planed surgery, RFA, Somatostatin Analogue, Sorafenib or Everolimus treatment
• signed informed consent

You may not qualify if:

• age below 18, concomitant invasive cancer (not skin cancer) and planed emigration of Denmark.

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Department of Hepatology and Gastroenterology

Aarhus, Aarhus C, 8000, Denmark

Location

Related Publications (16)

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  PMID: 24185511 BACKGROUND

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  PMID: 21252315 BACKGROUND

• 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 BACKGROUND

• 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.

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• 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.

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• 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 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples and biopsies when available.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neuroendocrine Tumors; Neoplastic Cells, Circulating

Interventions

Sorafenib; Radiofrequency Ablation; Everolimus; lanreotide; Octreotide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative; Sirolimus; Macrolides; Lactones; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jens Kelsen, Consultant

  Department of Hepatology and Gastroenterology, Aarhus University Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 25, 2016
• Study Start: November 1, 2016
• Primary Completion: January 8, 2020
• Study Completion: January 8, 2020
• Last Updated: April 28, 2021

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)