Circulating Tumor Cells and Tumor DNA in HCC and NET
Study Details
Study Description
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):
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Identify and isolate the CTC and investigate these for tumor-specific mutations.
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Quantify ctDNA and analyze this for specific mutations, which in the past has been found frequent in NET and HCC.
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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 | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| HCC sorafenib HCC patients referred for Sorafenib treatment |
Drug: Sorafenib
Other Names:
|
| 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:
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| 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:
|
Outcome Measures
Primary Outcome Measures
- Concordance between specific DNA mutations found in patient biopsies and plasma circulating tumor DNA [2 months]
Methods: digital droplet PCR and targeted sequencing of blood samples and biopsies
Secondary Outcome Measures
- 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]
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
- Correlations between mutations found in circulating tumor DNA and amount of circulating tumor cells and survival [up to 5 years]
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
- Correlations between mutations fund in circulating DNA and circulating tumor cells [3 years]
Methods: digital droplet PCR and targeted sequencing of blood samples, and flowcytometry and cell separation of blood samples
Eligibility Criteria
Criteria
Inclusion Criteria:
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one of the above mentioned diseases
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planed surgery, RFA, Somatostatin Analogue, Sorafenib or Everolimus treatment
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signed informed consent
Exclusion Criteria:
- age below 18, concomitant invasive cancer (not skin cancer) and planed emigration of Denmark.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hepatology and Gastroenterology | Aarhus | Aarhus C | Denmark | 8000 |
Sponsors and Collaborators
- University of Aarhus
- Aarhus University Hospital
Investigators
- Study Chair: Jens Kelsen, Consultant, Department of Hepatology and Gastroenterology, Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
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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.
- 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.
- 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.
- 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.
- Schulze K, Imbeaud S, Letouzé 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.
- 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.
- 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. Review.
- SK-HCC-NET