Silicon Microsieve Device vs Cell Surface Marker-based Platform for the Isolation of Pancreatic Cancer CTCs

Sponsor

Singapore General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04638868

Collaborator

Agency for Science, Technology and Research (Other)

Enrollment

Arm

13.4

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The study aims to compare the use of a microsieve device vs a cell surface marker-based platform for the isolation of pancreatic cancer circulating tumor cells

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Device: Microsieve device Device: Cell surface marker-based platform	N/A

Detailed Description

Circulating tumor cells (CTCs) aid prognostication of cancer by predicting the presence of microscopic metastases. This is important in pancreatic cancer, which is associated with a poor prognosis even in resectable disease, due to microscopic metastases that are not detectable on pre-operative cross-sectional imaging. In pancreatic cancer, blood is sampled from the portal circulation to overcome the "hepatic sieve" effect, where CTCs are filtered out in the capillary beds of the liver before entering the peripheral circulation. Minimally invasive blood sampling from the portal vein can now be done via endoscopic ultrasound (EUS) guidance, allowing CTC analyses to be done pre-operatively.

CTCs have traditionally been isolated in various cancers using a cell surface marker-based platform (CellSearch™). This involves the use of antibodies to identify, isolate and quantify CTCs based on presence of specific epithelial cell markers. However, CTCs are now known to undergo epithelial-mesenchymal transformation. The current epithelial cell surface marker-based method of CTC isolation is limited by its inability to detect mesenchymal-type CTCs, potentially under estimating the CTC count, affecting quantification and subsequent CTC molecular analyses.

The use of a novel silicon microsieve device will overcome these limitations. It will simplify the isolation of CTCs by its characteristic size, enable both epithelial and mesenchymal types of CTCs to be isolated and results in greater cell viability, aiding in subsequent cell culture and organoid growth.

The investigators will compare a novel silicon microsieve size-based cell filtration device against the cell surface marker label-based CellSearch™ platform for the identification of pancreatic cancer CTCs in portal venous blood obtained via an Endoscopic Ultrasound (EUS)-guided puncture. The investigators will compare the yield of epithelial-type CTCs isolated using both methods. The investigators will investigate whether the isolation of mesenchymal-type CTCs via a sized-based cell filtration device leads to a significant increase in total CTC yield.

The investigators expect our study to show that the new technique of size-based CTC isolation improves CTC yield in pancreatic cancer. This preliminary data would be crucial for future research into patient selection for neoadjuvant chemotherapy and individualized treatment from patient-specific tumor tissue, which the investigators intend to embark upon.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

A Head-to-head Comparison of a Novel Silicon Microsieve Device Against a Cell Surface Marker-based Platform for the Isolation of Portal Vein Circulating Tumor Cells in Pancreatic Cancer

Anticipated Study Start Date :

Nov 17, 2020

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isolation of circulating tumor cells Both portal venous and peripheral blood will be obtained from the patient and subjected to analysis for pancreatic cancer circulating tumor cells	Device: Microsieve device Both portal venous and peripheral blood will be processed through a label-free size-based silicon microsieve microfiltration device, which will isolate both epithelial-type and mesenchymal-type pancreatic cancer circulating tumor cells. Downstream mutational analyses will be performed to confirm identity of the cells. Device: Cell surface marker-based platform Both portal venous and peripheral blood will be processed through a cell surface marker-based platform, which contains antibodies for epithelial cell markers on pancreatic cancer circulating tumor cells. Downstream mutational analyses will be performed to confirm identity of the cells.

Arm

Intervention/Treatment

Experimental: Isolation of circulating tumor cells

Both portal venous and peripheral blood will be obtained from the patient and subjected to analysis for pancreatic cancer circulating tumor cells

Device: Microsieve device

Both portal venous and peripheral blood will be processed through a label-free size-based silicon microsieve microfiltration device, which will isolate both epithelial-type and mesenchymal-type pancreatic cancer circulating tumor cells. Downstream mutational analyses will be performed to confirm identity of the cells.

Device: Cell surface marker-based platform

Both portal venous and peripheral blood will be processed through a cell surface marker-based platform, which contains antibodies for epithelial cell markers on pancreatic cancer circulating tumor cells. Downstream mutational analyses will be performed to confirm identity of the cells.

Outcome Measures

Primary Outcome Measures

Number of circulating tumor cells [Immediately following procedure]
The number of circulating tumor cells isolated via both methods (microsieve device and cell surface marker-based platform)

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 21 years and older
All inpatients with solid pancreatic lesions referred for Endoscopic Ultrasound - Fine Needle Aspiration (EUS-FNA)
Solid lesions confirmed by at least a single investigational modality, mainly CT, MRI or endoscopy
Able to comply with the study procedure and provide informed consent.

Exclusion Criteria:

Presence of active bleeding
Presence of coagulopathy as evidenced by INR >1.5 and platelets <50,000
Poor patient tolerance to procedure
Concurrent intake of anticoagulants and thienopyridine (e.g.Clopidogrel) in patients who require antiplatelet therapy
Pregnancy
Presence of portal vein thrombus
Patients with liver cirrhosis and /or other structural abnormalities in the liver or the stomach