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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by The Netherlands Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Otilia Dalesio, The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT01713699
First received: October 22, 2012
Last updated: NA
Last verified: October 2012
History: No changes posted
  Purpose

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.


Condition Intervention
Meningeal Carcinomatosis
Procedure: lumbar puncture

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • - 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 ] [ Designated as safety issue: No ]
  • - 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 ] [ Designated as safety issue: No ]
  • - To determine the relationships between demographics/tumor status and CTCs number in CSF. [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
  • - 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 ] [ Designated as safety issue: No ]
  • To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF. [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
  • - To compare the predictive value of two CTC enumeration methods [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Procedure: lumbar puncture

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713699

Contacts
Contact: D. Brandsma, MD, PhD +31 (0)205122570
Contact: B. Milojkovic Kerklaan, MD

Locations
Netherlands
Dutch Cancer Institute - Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066CX
Contact: D. Brandsma, MD, PhD         
Principal Investigator: D Brandsma, MD, PhD         
Slotervaart Hospital Recruiting
Amsterdam, Netherlands, 1066EC
Contact: D. Brandsma, MD, PhD         
Principal Investigator: D. Brandsma, MD, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Investigators
Principal Investigator: D. Brandsma, MD, PhD NKI-AvL
  More Information

No publications provided

Responsible Party: Otilia Dalesio, PhD, The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT01713699     History of Changes
Other Study ID Numbers: N12CLM
Study First Received: October 22, 2012
Last Updated: October 22, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by The Netherlands Cancer Institute:
CTC, cytology, meningeal carcinomatosis, leptomeningeal metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplastic Cells, Circulating
Meningeal Carcinomatosis
Neoplastic Processes
Neoplasms
Pathologic Processes
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on September 18, 2014