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Circulating Tumor DNA in Cerebrospinal Fluid as an Early Biomarker of Leptomeningeal Metastasis (LM)

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ClinicalTrials.gov Identifier: NCT02071056
Recruitment Status : Active, not recruiting
First Posted : February 25, 2014
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
Lara K. Ronan, Dartmouth-Hitchcock Medical Center

Brief 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. The researchers doing this study hope this information can be used to develop a way to diagnose LM earlier .

Condition or disease
Leptomeningeal Metastasis

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 Type : Observational
Actual Enrollment : 5 participants
Observational Model: Case-Only
Time Perspective: Prospective
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
Actual Study Start Date : May 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Group/Cohort
history of visceral cancer



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Comparison of circulating tumor DNA levels in CSF with levels in plasma. [ Time Frame: one year ]
    To determine whether circulating tumor DNA levels in CSF correlate with levels in plasma.

  2. Correlation of circulating tumor DNA levels and patient survival. [ Time Frame: one year ]
    To determine whether circulating tumor DNA levels are predictive of patient survival.

  3. Circulating tumor DNA detection in CSF of patients with cytological evidence of leptomeningeal metastasis. [ Time Frame: one year ]
    To determine whether circulating tumor DNA is detectable in CSF of patients with cytological evidence of leptomeningeal metastasis.

  4. Circulating tumor DNA identification in the CSF of patients prior to diagnosis of leptomeningeal metastasis. [ Time Frame: one year ]
    To determine whether circulating tumor DNA can be identified in the CSF of patients prior to diagnosis of leptomeningeal metastasis.

  5. Measurement of circulating tumor DNA levels and cancer cell numbers in CSF following initiation of intrathecal chemotherapy for leptomeningeal metastasis. [ Time Frame: one year ]

Biospecimen Retention:   Samples With DNA
CSF and serum


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Neurology and Medical Oncology clinical practices
Criteria

Inclusion Criteria:

  1. 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).
  2. Age ≥ 18 years.
  3. 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.
  4. 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.
  5. Patient must consent to permit genetic analysis of their cancer.
  6. Patient capable of giving informed consent.
  7. 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.

Exclusion Criteria:

  1. Evidence of a CNS mass creating mass‐effect or midline shift such that lumbar puncture is contraindicated.
  2. Previous or current hematological malignancy.
  3. Previous or current primary CNS malignancy.
  4. Prior treatment for CNS metastasis.
  5. Known CNS autoimmune or inflammatory disease (i.e., Multiple Sclerosis, neurosarcoidosis, chronic fungal, rickettsial or bacterial meningitis).
  6. Patient is currently receiving treatment for LM.
  7. Patient was previously diagnosed with LM.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02071056


Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Lara K Ronan, MD Dartmouth-Hitchcock Medical Center

Responsible Party: Lara K. Ronan, Assistant Professor Neuro-Oncology, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT02071056     History of Changes
Other Study ID Numbers: D13237
First Posted: February 25, 2014    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: July 2018

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