Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases

Meningeal Carcinomatosis Clinical Trial

Official title:

Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01713699
• Other study ID #: N12CLM
• Status: Completed
• Phase: N/A
• Start date: September 2012
• Est. completion date: September 19, 2017

Study information

• Verified date: January 2021
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the quantitative detection of circulating tumor cells (CTCs) in patients with Epcam expressing tumors can be used compared to standard qualitative method - cytology both in the cerebrospinal fluid of patients, clinically suspected for leptomeningeal metastases.

Description:

Leptomeningeal metastases (LM), is a diffuse dissemination of tumor cells into the cerebrospinal fluid (CSF) and leptomeninges.[1] Up to 8% of all patients with cancer develop LM. Gadolinium enhanced MRI of the symptomatic location of the nervous system is the radiological method of choice when LM is clinically suspected. In patients with a metastasized tumor, based on clinical signs of LM and contrast enhancement of either the leptomeninges, pia mater/cortex or cranial or spinal nerves on MRI, the diagnosis LM can be made. The sensitivity of MRI with gadolineum for LM is 75% and the specificity 77%. If MRI does not show equivocal abnormalities, CSF cytology needs to be performed. In 55% of patients with LM from solid tumors, malignant cells are found during the first CSF examination. The sensitivity raises to 80-90% after the second CSF sampling, as determined in the pre-MRI era. The volume of sampled CSF determines partly the sensitivity of CSF cytology. If possible, 10 ml CSF needs to be taken and the material must be processed as quickly as possible.

Recently, Patel et al (2011) described the detection of breast cancer cells in the CSF using the Cell Search System (Veridex). [6] Using this method, the CSF is enriched immuno-magnetically for the epithelial cell adhesion molecule (EpCAM). Next nuclear staining with 4 ',6-diamidino-2-phenylindole (DAPI) and immunofluorescent detection with cytokeratin and CD45 is performed in 5 patients with leptomeningeal metastases from breast cancer and approximately 104 circulating tumor cells (CTCs)in 7,5 ml CSF were found, using this method. There seemed to be an association between the number of CTCs and response to intrathecal administered chemotherapy in this small group of patients.

In the future, the determination of CTCs in the CSF could be a new quantitative method for the anti-tumor response assessment of systemic or intrathecal therapy (as opposed to CSF cytology, which is subjective and not a quantitative method). If the method shows greater sensitivity than CSF cytology and can reliably measure single tumor cells, the sensitivity of CSF examination in patients with a clinical suspicion of LM will increase. Possibly, this method can also be used to detect micrometastases in the CSF in patients without neurological symptoms, but with a high risk of CNS metastases.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: September 19, 2017
• Est. primary completion date: September 6, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients who are treated for advanced EpCam positive solid tumors (such as breast cancer, lung cancer, gastrointestinal cancer)

• Age >= 18 years;

• Able and willing to give written informed consent;

• WHO performance status (0, 1, 2, 3 or 4);

• Able and willing to undergo lumbar puncture and veni-puncture.

Exclusion Criteria:

• Lumbar puncture not clinically / diagnostically indicated

Related Conditions & MeSH terms

• Carcinoma
• Meningeal Carcinomatosis
• Neoplasm Metastasis
• Neoplastic Cells, Circulating

Intervention

Procedure:
• lumbar puncture

Locations

Country	Name	City	State
Netherlands	Dutch Cancer Institute - Antoni van Leeuwenhoek	Amsterdam
Netherlands	Slotervaart Hospital	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the sensitivity and specificity of detection of circulating tumor cells (CTCs) in patients with Epcam expressing tumors compared to cytology in the cerebrospinal fluid of patients, clinically suspected for leptomeningeal metastases		3 months after end of study
Secondary	- To determine the relationship between the number of CTCs in CSF and the patient's neurological condition and WHO performance score		3 months after end of study
Secondary	- To determine the change in the CTC number between two sampling points and correlate this with the patient's neurological condition and therapy		3 months after end of study
Secondary	- To determine the relationships between demographics/tumor status and CTCs number in CSF.		3 months after end of study
Secondary	- To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood		3 months after end of study
Secondary	To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF.		3 months after end of study
Secondary	- To compare the predictive value of two CTC enumeration methods		3 months after end of study

External Links

•   NKI-AVL