The Utility of Circulating Tumour Cells and Plasma microRNA in Esophageal Adenocarcinoma

Esophageal Cancer Clinical Trial

Official title:

The Utility of Circulating Tumour Cells and Plasma microRNA Detection to Predict the Response to Treatment in Patients With Esophageal Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02812680
• Other study ID #: 15-9303-CE
• Status: Completed
• Start date: June 2016
• Est. completion date: November 2020

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Circulating microRNA (circ miRNA) and circulating tumor cell (CTC) levels are hypothesized to be associated with response to chemoradiation in patients undergoing treatment for locally advanced esophageal adenocarcinoma.

The goal of this project is to assess the use of circulating microRNA (miRNA) and circulating tumour cells (CTC) as biomarkers of cancer and predictive markers for neoadjuvant therapy.

Description:

Recently, different groups have discovered that miRNAs can be detected in body fluids such as plasma, serum or saliva. These cell-free miRNAs are secreted by cells under different forms. Levels of these circulating miRNAs (circ miRNA), like tissue miRNA, were closely related to pathologies and could be used as diagnostic or prognostic tools for several pathologies, including cancer. Furthermore, a recent report showed that circ miRNAs released by tumor cells have the ability to transfer their metastatic potential to nonmetastatic cells. The detection and analysis of circulating miRNA represent a new step towards non-invasive diagnostic screening and early cancer detection.

Circulating tumor cells also hold promise as biological markers, which can be assessed noninvasively. As more than 90% of cancer deaths are associated with metastasis, it is crucial to understand the mechanisms of dissemination of cancer cells. During the past decade, a multitude of techniques have been developed to track down and to characterize CTC. Clinical studies in various cancers reveal the potential of CTC as prognostic and predictive markers. The characterization of CTC will help to design personalized treatment to eradicate the sub-clones of the primary tumour, which give rise to metastasis. Also, the numbers of CTC in patient blood can be followed to monitor the efficacy of the neoadjuvant treatment.

Most of the research in esophageal cancer has been done on squamous cell cancer as this is the dominant cell type worldwide. However, beginning the in 1980s Esophageal Adenocarcinoma (EAC) has increased in frequency such that it now represents 80% of esophageal cancer in North America and Europe. There is an urgent need to develop new techniques and diagnostic tests to combat EAC. By combining circ miRNA and CTC, we not only combine 2 promising clinical biomarkers, we will also be able to access new data that will complement tissue biopsy data. Furthermore, by acquiring a blood sample during various time points of patient treatment, we will be able to create a dynamic CTC and circ miRNA profile.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: November 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients who are at least 18 years of age

• Patients with Esophageal Adenocarcinoma who will undergo neo-adjuvant therapy with surgical resection.

• Patients with esophageal adenocarcinoma who will be treated with chemotherapy, chemotherapy and radiation or radiation alone OR

• Healthy volunteers who are at least 18 years of age

Exclusion Criteria:

• Patients who are treated with surgery alone for esophageal cancer

• Patients who have a history of invasive cancer

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Cancer
• Neoplastic Cells, Circulating

Intervention

Other:
• Blood Draw
Blood draw to assess the use of circulating microRNA (miRNA) and circulating tumour cells (CTC) as biomarkers of cancer and predictive markers for neoadjuvant therapy.

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (26)

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23;116(2):281-97. doi: 10.1016/s0092-8674(04)00045-5. — View Citation

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009 Jan 23;136(2):215-33. doi: 10.1016/j.cell.2009.01.002. — View Citation

Blot WJ. Esophageal cancer trends and risk factors. Semin Oncol. 1994 Aug;21(4):403-10. — View Citation

Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006 Nov;6(11):857-66. doi: 10.1038/nrc1997. — View Citation

Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011 Jun 7;8(8):467-77. doi: 10.1038/nrclinonc.2011.76. — View Citation

Davies AR, Gossage JA, Zylstra J, Mattsson F, Lagergren J, Maisey N, Smyth EC, Cunningham D, Allum WH, Mason RC. Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol. 2014 Sep 20;32(27):2983-90. doi: 10.1200/JCO.2014.55.9070. — View Citation

Demeester SR. Epidemiology and biology of esophageal cancer. Gastrointest Cancer Res. 2009 Mar;3(2 Suppl):S2-5. — View Citation

Derouet MF, Liu G, Darling GE. MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance. PLoS One. 2014 Dec 31;9(12):e115589. doi: 10.1371/journal.pone.0115589. eCollection 2014. — View Citation

Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006 Apr;6(4):259-69. doi: 10.1038/nrc1840. — View Citation

Flynt AS, Lai EC. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet. 2008 Nov;9(11):831-42. doi: 10.1038/nrg2455. — View Citation

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013. — View Citation

Joosse SA, Gorges TM, Pantel K. Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol Med. 2015 Jan;7(1):1-11. doi: 10.15252/emmm.201303698. — View Citation

Knox JJ, Wong R, Visbal AL, Horgan AM, Guindi M, Hornby J, Xu W, Ringash J, Keshavjee S, Chen E, Haider M, Darling G. Phase 2 trial of preoperative irinotecan plus cisplatin and conformal radiotherapy, followed by surgery for esophageal cancer. Cancer. 2010 Sep 1;116(17):4023-32. doi: 10.1002/cncr.25349. — View Citation

Ko MA, Zehong G, Virtanen C, Guindi M, Waddell TK, Keshavjee S, Darling GE. MicroRNA expression profiling of esophageal cancer before and after induction chemoradiotherapy. Ann Thorac Surg. 2012 Oct;94(4):1094-102; discussion 1102-3. doi: 10.1016/j.athoracsur.2012.04.145. Epub 2012 Aug 29. — View Citation

Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. Molecular analysis of circulating tumour cells-biology and biomarkers. Nat Rev Clin Oncol. 2014 Mar;11(3):129-44. doi: 10.1038/nrclinonc.2013.253. Epub 2014 Jan 21. — View Citation

Lawrie CH, Cooper CD, Ballabio E, Chi J, Tramonti D, Hatton CS. Aberrant expression of microRNA biosynthetic pathway components is a common feature of haematological malignancy. Br J Haematol. 2009 May;145(4):545-8. doi: 10.1111/j.1365-2141.2009.07642.x. Epub 2008 Mar 2. No abstract available. — View Citation

Le MT, Hamar P, Guo C, Basar E, Perdigao-Henriques R, Balaj L, Lieberman J. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest. 2014 Dec;124(12):5109-28. doi: 10.1172/JCI75695. Epub 2014 Nov 17. — View Citation

Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8. doi: 10.1073/pnas.0804549105. Epub 2008 Jul 28. — View Citation

Mohamadi RM, Besant JD, Mepham A, Green B, Mahmoudian L, Gibbs T, Ivanov I, Malvea A, Stojcic J, Allan AL, Lowes LE, Sargent EH, Nam RK, Kelley SO. Nanoparticle-mediated binning and profiling of heterogeneous circulating tumor cell subpopulations. Angew Chem Int Ed Engl. 2015 Jan 2;54(1):139-43. doi: 10.1002/anie.201409376. Epub 2014 Nov 5. — View Citation

Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, Wong DT. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009 Sep 1;15(17):5473-7. doi: 10.1158/1078-0432.CCR-09-0736. Epub 2009 Aug 25. — View Citation

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108. doi: 10.3322/canjclin.55.2.74. — View Citation

Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009 Jan;112(1):55-9. doi: 10.1016/j.ygyno.2008.08.036. Epub 2008 Oct 26. — View Citation

Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, Konishi H, Morimura R, Deguchi K, Fujiwara H, Okamoto K, Otsuji E. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010 Mar 30;102(7):1174-9. doi: 10.1038/sj.bjc.6605608. Epub 2010 Mar 16. — View Citation

Turchinovich A, Weiz L, Burwinkel B. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem Sci. 2012 Nov;37(11):460-5. doi: 10.1016/j.tibs.2012.08.003. Epub 2012 Sep 1. — View Citation

Underwood TJ, Derouet MF, White MJ, Noble F, Moutasim KA, Smith E, Drew PA, Thomas GJ, Primrose JN, Blaydes JP. A comparison of primary oesophageal squamous epithelial cells with HET-1A in organotypic culture. Biol Cell. 2010 Dec;102(12):635-44. doi: 10.1042/BC20100071. — View Citation

Underwood TJ, Hayden AL, Derouet M, Garcia E, Noble F, White MJ, Thirdborough S, Mead A, Clemons N, Mellone M, Uzoho C, Primrose JN, Blaydes JP, Thomas GJ. Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma. J Pathol. 2015 Feb;235(3):466-77. doi: 10.1002/path.4467. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating microRNA (miRNA) as biomarkers of cancer and predictive markers for neoadjuvant therapy by using Human miRNA cards		2 years
Primary	Circulating tumour cells (CTC) as biomarkers of cancer and predictive markers for neoadjuvant therapy by using CTC chips		2 years

External Links

•   Canadian Cancer Statistics 2010