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

NCT02071056 | Completed DMC

• 1 other identifier: D13237
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

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 .

Conditions

Leptomeningeal Metastasis

Outcome Measures

Primary Outcomes (1)

• 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

  one year

Secondary Outcomes (5)

• Comparison of circulating tumor DNA levels in CSF with levels in plasma.

  one year

• Correlation of circulating tumor DNA levels and patient survival.

  one year

• Circulating tumor DNA detection in CSF of patients with cytological evidence of leptomeningeal metastasis.

  one year

• Circulating tumor DNA identification in the CSF of patients prior to diagnosis of leptomeningeal metastasis.

  one year

• Measurement of circulating tumor DNA levels and cancer cell numbers in CSF following initiation of intrathecal chemotherapy for leptomeningeal metastasis.

  one year

Study Arms (1)

history of visceral cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Neurology and Medical Oncology clinical practices

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

CSF and serum

MeSH Terms

Conditions

Meningeal Carcinomatosis

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• Lara K Ronan, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Neuro-Oncology

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: February 25, 2014
• Study Start: May 1, 2014
• Primary Completion: November 25, 2015
• Study Completion: November 25, 2015
• Last Updated: August 18, 2020

Record last verified: 2020-08

Locations

US (1)