Leptomeningeal MetastasisNCT02071056
Circulating Tumor DNA in Cerebrospinal Fluid as an Early Biomarker of Leptomeningeal Metastasis (LM)
An observational study of Leptomeningeal Metastasis, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to learn whether the DNA from cancer tumor cells can be found in the cerebral spinal fluid (CSF) that bathes the brain and spinal cord of patients before malignant the cancer cells themselves are able to be found in the CSF. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Metastasis
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to 25 Nov 2015
- Phase
- Observational
- 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
Study population: Neurology and Medical Oncology clinical practices
Who may be able to join
- Patient must have a previously diagnosed solid tumor malignancy originating from a visceral organ (i.e., outside of the CNS), and present with signs and/or symptoms consistent with carcinomatous meningitis (headache, vision dysfunction, hearing loss, cranial nerve deficit, cognitive dysfunction, focal weakness or numbness suggestive of cranial neuropathy or radiculopathy, cauda equine syndrome, meningismus, and/or bowel or bladder dysfunction).
- Age ≥ 18 years.
- Patients will meet accepted standard of care and follow FDA guidance for low molecular weight heparin use prior to lumbar puncture, specifically INR < 1.4 and PT within normal range for DHMC laboratory, and platelet count >50,000. For enoxaparin use, delay of Lumbar puncture to allow at least 12 hours after administration of prophylactic doses, such as those used for prevention of deep vein thrombosis. Longer delays (24 hours) are appropriate to consider for patients receiving higher therapeutic doses of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). A postprocedure dose of enoxaparin should usually be given no sooner than 4 hours after lumbar puncture. Aspirin and other antiplatelet therapy is permitted without timing constraints prior to or after lumbar puncture.
- Patient must consent to provide up to additional CSF (10 mL) and blood (10 mL) when these fluids are drawn as part of clinically indicated procedures.
- Patient must consent to permit genetic analysis of their cancer.
- Patient capable of giving informed consent.
- MRI of clinically symptomatic area (spine and/or brain) and/or head CT within the last 3 months to exclude brain disease that would contraindicate lumbar puncture.
Who cannot join
- Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated.
- Previous or current hematological malignancy.
- Previous or current primary CNS malignancy.
- Prior treatment for CNS metastasis.
- Known CNS autoimmune or inflammatory disease (i.e., Multiple Sclerosis, neurosarcoidosis, chronic fungal, rickettsial or bacterial meningitis).
- Patient is currently receiving treatment for LM.
- Patient was previously diagnosed with LM.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: Tissue and Fluid Collection Pilot Study to Develop Circulating Tumor DNA in Cerebrospinal Fluid as an Early Biomarker of LM in Patients With Metastatic Solid Tumor Cancer
The purpose of this study is to learn whether the DNA from cancer tumor cells can be found in the cerebral spinal fluid (CSF) that bathes the brain and spinal cord of patients before malignant the cancer cells themselves are able to be found in the CSF. The researchers doing this study hope this information can be used to develop a way to diagnose LM earlier .
Read the detailed description
The contents of dead/dying tumor cells can be detected in the bloodstream, and this may be enhanced by the leaky vasculature of solid tumors. Circulating tumor DNA has been detected in plasma from patients with osteosarcoma, breast cancer, and colorectal cancer, and in cerebrospinal fluid from patients with cancer-associated neoplastic meningitis. Until recently, it was impractical to develop an assay to routinely quantify circulating tumor DNA due to heterogeneity between patients and tumors. Advances in genomic technology now permit sequencing a tumor genome to identify patient-specific genomic aberrations. Major genomic alterations (i.e., insertions, amplifications, deletions, inversions, translocations) can be readily detected using PCR primers and probes which will recognize tumor DNA but not normal DNA, permitting creation of a personalized assay to quantify tumor DNA levels in bodily fluids. We therefore propose a pilot study to determine whether circulating tumor DNA levels increase in CSF prior to cytological evidence of LM in patients with a history of cancer originating from a visceral organ.
- Conditions
- Leptomeningeal Metastasis
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| history of visceral cancer | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor DNA detectability and cytological confirmation of leptomeningeal metastasis.
To determine whether circulating tumor DNA can be identified in the CSF of patients prior to cytological evidence of leptomeningeal metastasis in patients with a history of visceral cancer
Measured: one year
Secondary outcomes (5)
Comparison of circulating tumor DNA levels in CSF with levels in plasma.
To determine whether circulating tumor DNA levels in CSF correlate with levels in plasma.
Measured: one year
Correlation of circulating tumor DNA levels and patient survival.
To determine whether circulating tumor DNA levels are predictive of patient survival.
Measured: one year
Circulating tumor DNA detection in CSF of patients with cytological evidence of leptomeningeal metastasis.
To determine whether circulating tumor DNA is detectable in CSF of patients with cytological evidence of leptomeningeal metastasis.
Measured: one year
Circulating tumor DNA identification in the CSF of patients prior to diagnosis of leptomeningeal metastasis.
To determine whether circulating tumor DNA can be identified in the CSF of patients prior to diagnosis of leptomeningeal metastasis.
Measured: one year
Measurement of circulating tumor DNA levels and cancer cell numbers in CSF following initiation of intrathecal chemotherapy for leptomeningeal metastasis.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2014 (estimated)
- Study startMay 2014
- Primary completion25 Nov 2015
- Study completion25 Nov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal MetastasisStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lara K. Ronan, Dartmouth-Hitchcock Medical Center
- Investigators
- Lara K Ronan, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071056
- Sponsor's protocol ID
- D13237
- Status last verified
- Aug 2020
- First submitted
- 21 Feb 2014
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tissue and Fluid Collection Pilot Study to Develop Circulating Tumor DNA in Cerebrospinal Fluid as an Early Biomarker of LM in Patients With Metastatic Solid Tumor Cancer
- ClinicalTrials.gov ID
- NCT02071056
- Acronym / sponsor ID
- D13237
- Conditions
- Leptomeningeal Metastasis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- May 2014 (actual)
- Primary completion
- 25 Nov 2015 (actual)
- Study completion
- 25 Nov 2015 (actual)
- First posted
- 25 Feb 2014 (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 learn whether the DNA from cancer tumor cells can be found in the cerebral spinal fluid (CSF) that bathes the brain and spinal cord of patients before malignant the cancer cells themselves are able to be found in the CSF. The researchers doing this study hope this information can be used to develop a way to diagnose LM earlier .
Detailed description
The contents of dead/dying tumor cells can be detected in the bloodstream, and this may be enhanced by the leaky vasculature of solid tumors. Circulating tumor DNA has been detected in plasma from patients with osteosarcoma, breast cancer, and colorectal cancer, and in cerebrospinal fluid from patients with cancer-associated neoplastic meningitis. Until recently, it was impractical to develop an assay to routinely quantify circulating tumor DNA due to heterogeneity between patients and tumors. Advances in genomic technology now permit sequencing a tumor genome to identify patient-specific genomic aberrations. Major genomic alterations (i.e., insertions, amplifications, deletions, inversions, translocations) can be readily detected using PCR primers and probes which will recognize tumor DNA but not normal DNA, permitting creation of a personalized assay to quantify tumor DNA levels in bodily fluids. We therefore propose a pilot study to determine whether circulating tumor DNA levels increase in CSF prior to cytological evidence of LM in patients with a history of cancer originating from a visceral organ.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| history of visceral cancer | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Neurology and Medical Oncology clinical practices
Key inclusion criteria (7 listed)
- Patient must have a previously diagnosed solid tumor malignancy originating from a visceral organ (i.e., outside of the CNS), and present with signs and/or symptoms consistent with carcinomatous meningitis (headache, vision dysfunction, hearing loss, cranial nerve deficit, cognitive dysfunction, focal weakness or numbness suggestive of cranial neuropathy or radiculopathy, cauda equine syndrome, meningismus, and/or bowel or bladder dysfunction).
- Age ≥ 18 years.
- Patients will meet accepted standard of care and follow FDA guidance for low molecular weight heparin use prior to lumbar puncture, specifically INR < 1.4 and PT within normal range for DHMC laboratory, and platelet count >50,000. For enoxaparin use, delay of Lumbar puncture to allow at least 12 hours after administration of prophylactic doses, such as those used for prevention of deep vein thrombosis. Longer delays (24 hours) are appropriate to consider for patients receiving higher therapeutic doses of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). A postprocedure dose of enoxaparin should usually be given no sooner than 4 hours after lumbar puncture. Aspirin and other antiplatelet therapy is permitted without timing constraints prior to or after lumbar puncture.
- Patient must consent to provide up to additional CSF (10 mL) and blood (10 mL) when these fluids are drawn as part of clinically indicated procedures.
- Patient must consent to permit genetic analysis of their cancer.
Key exclusion criteria (7 listed)
- Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated.
- Previous or current hematological malignancy.
- Previous or current primary CNS malignancy.
- Prior treatment for CNS metastasis.
- Known CNS autoimmune or inflammatory disease (i.e., Multiple Sclerosis, neurosarcoidosis, chronic fungal, rickettsial or bacterial meningitis).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Tumor DNA detectability and cytological confirmation of leptomeningeal metastasis.
Time frame: one year
To determine whether circulating tumor DNA can be identified in the CSF of patients prior to cytological evidence of leptomeningeal metastasis in patients with a history of visceral cancer
5 secondary outcomes
Comparison of circulating tumor DNA levels in CSF with levels in plasma.
Time frame: one year
Correlation of circulating tumor DNA levels and patient survival.
Time frame: one year
Circulating tumor DNA detection in CSF of patients with cytological evidence of leptomeningeal metastasis.
Time frame: one year
Circulating tumor DNA identification in the CSF of patients prior to diagnosis of leptomeningeal metastasis.
Time frame: one year
Measurement of circulating tumor DNA levels and cancer cell numbers in CSF following initiation of intrathecal chemotherapy for leptomeningeal metastasis.
Time frame: one year
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 18 Aug 2020.
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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.
Lara K Ronan, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leptomeningeal Metastasis, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
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 7 inclusion and 7 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 18 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Tumor DNA detectability and cytological confirmation of leptomeningeal metastasis. (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Aug 2020.