Meningeal CarcinomatosisNCT01713699
Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
A study testing lumbar puncture in people with Meningeal Carcinomatosis, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Meningeal Carcinomatosis
- What is being tested?
- lumbar puncture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 2 sitesNetherlands
- Study dates
- Sep 2012to 19 Sep 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Lumbar puncture not clinically / diagnostically indicated
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Dutch Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, 1066CX
Slotervaart Hospital
Amsterdam, 1066EC
About this study
Official title: Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
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.
Read the 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.
- Conditions
- Meningeal Carcinomatosis
- Being tested
- lumbar puncture
- Keywords
- CTC, cytology, meningeal carcinomatosis, leptomeningeal metastases
- Medical subject headings
- Meningeal Carcinomatosis, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lumbar punctureProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| diagnostic | Other | 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. Receives: Procedure: lumbar puncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months after end of study
Secondary outcomes (6)
- To determine the relationship between the number of CTCs in CSF and the patient's neurological condition and WHO performance score
Measured: 3 months after end of study
- To determine the change in the CTC number between two sampling points and correlate this with the patient's neurological condition and therapy
Measured: 3 months after end of study
- To determine the relationships between demographics/tumor status and CTCs number in CSF.
Measured: 3 months after end of study
- To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood
Measured: 3 months after end of study
To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF.
Measured: 3 months after end of study
- To compare the predictive value of two CTC enumeration methods
Measured: 3 months after end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2012 (estimated)
- Study startSep 2012
- Primary completion6 Sep 2016
- Study completion19 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Meningeal CarcinomatosisStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- D. Brandsma, MD, PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713699
- Sponsor's protocol ID
- N12CLM
- Status last verified
- Jan 2021
- First submitted
- 22 Oct 2012
- Last updated
- 22 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Milojkovic Kerklaan B, Pluim D, Bol M, Hofland I, Westerga J, van Tinteren H, Beijnen JH, Boogerd W, Schellens JH, Brandsma D. EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors. Neuro Oncol. 2016 Jun;18(6):855-62. doi: 10.1093/neuonc/nov273. Epub 2015 Nov 12.
PubMed 26566655
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining the Sensitivity and Specificity of Circulating Tumor Cells and Cytology in Cerebrospinal Fluid of Patients Clinically Suspected for Leptomeningeal Metastases
- ClinicalTrials.gov ID
- NCT01713699
- Acronym / sponsor ID
- N12CLM
- Conditions
- Meningeal Carcinomatosis
- Keywords
- CTC, cytology, meningeal carcinomatosis, leptomeningeal metastases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- 6 Sep 2016 (actual)
- Study completion
- 19 Sep 2017 (actual)
- First posted
- 25 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| diagnostic | Other | Procedure: lumbar punctureUsing 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (1 listed)
- Lumbar puncture not clinically / diagnostically indicated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lumbar puncture | Procedure or surgery | diagnostic |
Primary outcome
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
6 secondary outcomes
- 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
- 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
- To determine the relationships between demographics/tumor status and CTCs number in CSF.
Time frame: 3 months after end of study
- 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
To confirm EPCAM positivity in archived primary tumor tissue and tumorcells in CSF.
Time frame: 3 months after end of study
- To compare the predictive value of two CTC enumeration methods
Time frame: 3 months after end of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Derived from this study: PubMed 26566655Milojkovic Kerklaan B, Pluim D, Bol M, Hofland I, Westerga J, van Tinteren H, Beijnen JH, Boogerd W, Schellens JH, Brandsma D. EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors. Neuro Oncol. 2016 Jun;18(6):855-62. doi: 10.1093/neuonc/nov273. Epub 2015 Nov 12.
- NKI-AVLLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
D. Brandsma, MD, PhD principal investigator
The Netherlands Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing lumbar puncture in people with Meningeal Carcinomatosis, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01713699, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.