- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01713699
Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Amsterdam, Netherlands, 1066CX
- Dutch Cancer Institute - Antoni van Leeuwenhoek
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Amsterdam, Netherlands, 1066EC
- Slotervaart Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: diagnostic
Using extra CSF material received by clinically indicated lumbar punctures to determine the sensitivity and specificity of CTCs in CSF (5ml CSF).
Standard material of 5 ml CSF for cytology and 2 ml CSF for cell count and chemistry is being regularly used and processed.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: 3 months after end of study
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3 months after end of study
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
- To determine the relationship between the number of CTCs in CSF and the patient's neurological condition and WHO performance score
Time Frame: 3 months after end of study
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3 months after end of study
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- To determine the change in the CTC number between two sampling points and correlate this with the patient's neurological condition and therapy
Time Frame: 3 months after end of study
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3 months after end of study
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- To determine the relationships between demographics/tumor status and CTCs number in CSF.
Time Frame: 3 months after end of study
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3 months after end of study
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- To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood
Time Frame: 3 months after end of study
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3 months after end of study
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To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF.
Time Frame: 3 months after end of study
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3 months after end of study
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- To compare the predictive value of two CTC enumeration methods
Time Frame: 3 months after end of study
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3 months after end of study
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: D. Brandsma, MD, PhD, NKI-AVL
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Meningeal Neoplasms
- Carcinoma
- Neoplasm Metastasis
- Neoplastic Cells, Circulating
- Meningeal Carcinomatosis
Other Study ID Numbers
- N12CLM
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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