Lumbar Punctures for Lung Cancer

Overseen By The Ohio State Comprehensive Cancer Center

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Disqualifiers: Alzheimer's, Dementia, Mental disability, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 1-2 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

How is the treatment Lumbar Puncture unique for lung cancer?

Lumbar puncture is unique for lung cancer as it allows for the collection of cerebrospinal fluid (CSF), which can be used as a liquid biopsy to detect genetic mutations and drug resistance in leptomeningeal metastases (cancer spread to the membranes surrounding the brain and spinal cord). This approach provides a non-invasive way to gather important genetic information that can guide treatment decisions, especially when direct access to the cancerous lesions is limited. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial assesses the use of lumbar punctures to detect whether there is circulating tumor deoxyribonucleic acid (ctDNA) in the fluid that surrounds the brain and spinal cord (cerebrospinal fluid) in patients with stage III and IV non-small cell lung cancer (NSCLC). Patients with stage III and IV NSCLC are at risk of having their cancer spread from where it first started to the brain (metastatic). Because of this, more effective prognostic tools are necessary to determine which stage III and IV NSCLC patients are more likely to develop brain metastases. Cerebrospinal fluid (CSF) could be a reliable source of ctDNA to confirm and predict the presence of brain metastases in these patients. Assessing cell free DNA shed from tumor cells could be a sensitive and minimally invasive way to detect or characterize metastatic tumors in the central nervous system (CNS). Lumbar puncture is procedure in which a thin needle called a spinal needle is put into the lower part of the spinal column to collect CSF. Lumbar punctures for the collection of CSF may help doctors detect or measure changes in cell types, genes, and proteins of circulating tumor cells related to lung cancer that will help determine the presence of brain metastases which could become a standard of care screening tool utilized in the follow-up of patients diagnosed with stage II or IV NSCLC.

Research Team

Joshua D Palmer, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for patients with advanced non-small cell lung cancer (stages III and IV). It's designed to see if a procedure called lumbar puncture can detect tumor DNA in spinal fluid, which might help predict brain metastases. Participants should be at risk of their cancer spreading to the brain.

Inclusion Criteria

Estimated survival >= 1 year

My lung cancer is at an advanced stage (III or IV).

My advanced lung cancer has a specific mutation identified by a test.

Exclusion Criteria

Previous cancer history prior to diagnosis of NSCLC

Patient has Alzheimer's, dementia, or mental disability

I cannot undergo an MRI scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients undergo lumbar puncture for collection of CSF and blood sample collection, and MRI during screening

1-2 weeks

1 visit (in-person)

Follow-up

Patients are monitored for ctDNA presence and undergo additional lumbar puncture if necessary; MRI performed at 6 months for Cohort 1

6-12 months

2-3 visits (in-person)

Long-term follow-up

Patients without brain metastases are followed for 12 months, while those with brain metastases are followed for 6 months

6-12 months

Treatment Details

Interventions

• Lumbar Puncture

Trial Overview The study is testing whether lumbar punctures can find circulating tumor DNA in cerebrospinal fluid as a way to foresee brain metastasis in stage III and IV NSCLC patients. The trial includes MRI scans and biospecimen collection for analysis.

Participant Groups

Group I: Cohort 2: Stage IV NSCLC with brain metastases (LP) Experimental Treatment 3 Interventions

Patients undergo LP for collection of CSF and blood sample collection on study. Patients also undergo MRI during screening. Patients with CSF negative for ctDNA at the first LP draw, undergo an additional LP draw at 6 months. Patients with CSF positive for ctDNA at the first LP draw, may not undergo an additional LP at 6 months.

Group II: Cohort 1: Stage III/IV without brain metastases (LP) Experimental Treatment 3 Interventions

Patients undergo LP for collection of CSF and blood sample collection after completion of chemoradiotherapy (stage III) or after diagnosis (stage IV) on study. Patients also undergo MRI during screening and 12 month follow-up. Patients with CSF negative for ctDNA at the first LP draw, undergo an additional LP draw at 6 months. Patients with CSF positive for ctDNA at the first LP draw, may not undergo an additional LP at 6 months.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) was found to be a highly effective source for detecting genetic mutations in patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC), with 100% detection of driver genes in CSF cfDNA samples.

The study revealed that CSF cfDNA not only captured unique genetic profiles compared to plasma and primary tumor samples but also showed a significantly higher frequency of copy number variations and loss of heterozygosity in key genes like TP53, indicating its potential as a superior liquid biopsy medium for monitoring LM in patients with EGFR mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy. Li, YS., Jiang, BY., Yang, JJ., et al.[2020]

This case study highlights the successful use of next-generation sequencing (NGS) of cerebrospinal fluid (CSF) to identify an uncommon EGFR mutation (G719A) in a 34-year-old male patient with non-small cell lung cancer (NSCLC) and leptomeningeal metastases, which was not detected in peripheral blood.

The patient showed significant clinical improvement and a good response to afatinib therapy over 7 months, demonstrating the efficacy of targeted therapy guided by CSF genetic testing, which proved to be more effective than blood testing in this scenario.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid. Ma, C., Huang, C., Tang, D., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebrospinal Fluid Cell-Free DNA-Based Detection of High Level of Genomic Instability Is Associated With Poor Prognosis in NSCLC Patients With Leptomeningeal Metastases. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid. [2023]

4. Singapore pubmed.ncbi.nlm.nih.gov

Genotyping of cerebrospinal fluid in lung cancer patients with leptomeningeal metastasis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The diagnostic significance of cerebrospinal fluid cytology and circulating tumor DNA in meningeal carcinomatosis. [2023]