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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT04239105
Other study ID # Yuan Shifang-1
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date January 2020
Est. completion date December 2022

Study information

Verified date January 2020
Source Xijing Hospital
Contact Shifang Yuan, professor
Phone 13991249382
Email shifangy@fmmu.edu.cn
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Circulating tumor cells (CTCs) in peripheral blood originate from breast cancer (primary and metastatic lesions) shedding. Utilization of CTCs as novel and noninvasive tests for diagnosis confirmation, therapy selection, and cancer surveillance is a rapidly growing area of interest. In this project, the investigators will explore a novel detection technology of circulating tumor cells in breast cancer using novel Microfluidic and Raman Spectrum Device. The primary objective is to demonstrate that the CTC assay counts technology can distinguish between healthy subjects and malignant breast cancer subjects. The secondary objective is to demonstrate that the CTCs detection technology can evaluate the efficacy of chemotherapy and neoadjuvant chemotherapy, as well as dynamic treatment monitoring and prognosis evaluation.


Description:

Circulating tumor cells (CTCs) are a new type of breast cancer molecular marker. CTCs in peripheral blood originate from breast cancer (primary and metastatic lesions) shedding. Utilization of CTCs as novel and noninvasive tests for diagnosis confirmation, therapy selection, and cancer surveillance is a rapidly growing area of interest. At present, there is a great challenge to create an effective platform that can isolate these cells, as they are extremely rare: only 1-10 CTCs are present in a 7.5mL of a cancer patient's peripheral blood. The majority of the CTC capture methods are based on EpCAM expression as a surface marker of tumor-derived cells. However, EpCAM protein expression levels can be significantly down regulated during cancer progression as a consequence of the process of epithelial to mesenchymal transition. Although many technologies have been reported to achieve the capture and counting of CTCs, these methods study little information of cells and limited biological information can be obtained, leading to a lack in clinical diagnosis.

Microfluidics has demonstrated great potential as an effective technique for the medical and biological sciences. Inspired by the bed topography in river meanders, here, the investigators report a novel river meander-like cross-section in helical microchannels for size-based inertial focusing and enrichment, aiming to realize more functional geometries as well as reduce the extensive laborious requirement in traditional fabrication process. This device can facilitate particle focusing at a larger scale than traditional channels. Compared to the circular, rectangular and trapezoidal channels, the river meander-like microfluidic channel can successfully realize 26 μm particle focusing with a thinner focusing band in a shorter channel length. Also, in a single test, this structure can achieve 85.4% recovery and the enrichment ratio of 1.86 of spiked MDA-MB-231 cells in the whole blood, overcoming the dependence on traditional cell manipulation microfluidic devices. These results indicate that this river meander-like microfluidic chip has the great potential of size-based cell/particle sorting and enrichment for clinical application. Meanwhile, Surface-enhanced Raman scattering (SERS) has such advantages as high sensitivity, flexible excitation wavelength, high spectral resolution, non-invasiveness to biological samples, resistance self-fluorescence, photobleaching, etc., which is considered as a promising and powerful real-time detection technology for unlabeled cells. But SERS spectrum of cell contains information about different molecules, so it usually requires complex data interpretation. Therefore, the application of Raman spectroscopy combined with chemometrics in biological problems has attracted more and more attention. However, analysis result of chemometrics can be influenced by the complex background of Raman spectroscopy. Therefore, a pre-processing is needed to remove these influencing factors.

Based on these previous work, the investigators have developed a novel technology for the detection of CTCs of breast cancer. The detection platform constructed by the combination of microfluidic chip and surface-enhanced Raman spectroscopy is used to detect the blood sample of the subject, obtain the high quality of breast cancer circulating tumor cells from the aspects of cell specificity, surface structure and molecular activity of surface-enhanced Raman spectrum information, and extract the characteristics of different breast cancer circulating tumor cells by related signal feature extraction methods, establish a standard surface-enhanced Raman spectral feature database for the main types of breast cancer circulating tumor cells.

This technology aims to build a platform allowing for cell detection, synthesize particles for surface plasmon Raman enhancement, fabricate microfluidic devices, study the collection and analysis of the Raman spectra of CTCs, establish the database of CTC Raman spectra and develop the evaluation method of the biological detection. The primary objective is to demonstrate that the CTC assay counts technology can distinguish between healthy subjects and malignant breast cancer subjects. The secondary objective is to demonstrate that the CTCs detection technology can evaluate the efficacy of chemotherapy and neoadjuvant chemotherapy, as well as dynamic treatment monitoring and prognosis evaluation.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 120
Est. completion date December 2022
Est. primary completion date July 2021
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 20 Years to 70 Years
Eligibility Inclusion Criteria:

- All subjects need to sign the informed consent form.

- Age of at least 20 and at most 70 years.

- Cancer group subjects with pathology report confirmed to be malignant.

- Chemotherapy is necessary before or after surgery.

- Control group need to have mammogram /ultrasound results category1-3.

- Patients must be available for and compliant to treatment and follow-up.

Exclusion Criteria:

- Not willing to sign the informed consent form.

- Pregnant or lactating patients.

- Prior or concomitant secondary malignancy.

- Any other serious medical pathology, such as congestive heart failure.

- Other condition which may affect the CTC results.

- Males.

Study Design


Intervention

Device:
Microfluidic and Raman spectrum
Detection of Circulating Tumor Cells

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Xijing Hospital Xidian University

References & Publications (37)

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Poudineh M, Aldridge PM, Ahmed S, Green BJ, Kermanshah L, Nguyen V, Tu C, Mohamadi RM, Nam RK, Hansen A, Sridhar SS, Finelli A, Fleshner NE, Joshua AM, Sargent EH, Kelley SO. Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking. Nat Nanotechnol. 2017 Mar;12(3):274-281. doi: 10.1038/nnano.2016.239. Epub 2016 Nov 21. — View Citation

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Sun Y, Haglund TA, Rogers AJ, Ghanim AF, Sethu P. Review: Microfluidics technologies for blood-based cancer liquid biopsies. Anal Chim Acta. 2018 Jul 5;1012:10-29. doi: 10.1016/j.aca.2017.12.050. Epub 2018 Feb 3. Review. — View Citation

Taylor-Papadimitriou J, Burchell JM, Graham R, Beatson R. Latest developments in MUC1 immunotherapy. Biochem Soc Trans. 2018 Jun 19;46(3):659-668. doi: 10.1042/BST20170400. Epub 2018 May 21. Review. — View Citation

Thege FI, Lannin TB, Saha TN, Tsai S, Kochman ML, Hollingsworth MA, Rhim AD, Kirby BJ. Microfluidic immunocapture of circulating pancreatic cells using parallel EpCAM and MUC1 capture: characterization, optimization and downstream analysis. Lab Chip. 2014 May 21;14(10):1775-84. doi: 10.1039/c4lc00041b. Epub 2014 Mar 28. — View Citation

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Xu X, Zhao L, Xue Q, Fan J, Hu Q, Tang C, Shi H, Hu B, Tian J. Dynamic Liquid Surface Enhanced Raman Scattering Platform Based on Soft Tubular Microfluidics for Label-Free Cell Detection. Anal Chem. 2019 Jul 2;91(13):7973-7979. doi: 10.1021/acs.analchem.9 — View Citation

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* Note: There are 37 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary The level of CTC markers in breast cancer patients' peripheral blood The counts and analysis of CTC of peripheral blood in breast cancer group and healthy control group. 19 Months
Secondary The change of CTC markers in breast cancer patients' peripheral blood during chemotherapy and Neoadjuvant chemotherapy The counts and analysis of CTC in patients' peripheral blood during chemotherapy and Neoadjuvant chemotherapy in different periods. 17 Months
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