CSF Analysis for Non-Small Cell Lung Cancer

Overseen By Barbara Melosky, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Disqualifiers: Thrombocytopenia, Bleeding disorders, others

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

Compensation: Varies

Number of Visits: 26

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand molecular differences in cancer found in the brain compared to the rest of the body, specifically for individuals with non-small cell lung cancer (NSCLC) that has spread to the brain's protective layers (leptomeningeal disease). Participants will undergo a lumbar puncture (spinal tap) and a blood test to analyze tumor DNA. Eligible participants have NSCLC with a specific mutation (EGFR) and confirmed leptomeningeal disease. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to better understanding and treatment options for leptomeningeal disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that lumbar puncture and phlebotomy are safe for this trial?

Research has shown that a lumbar puncture, or spinal tap, is generally safe. One study found it effective for accessing spinal fluid in cancer patients. This procedure often diagnoses conditions like meningitis or cancer in the brain or spinal cord. Another study confirmed that patients usually tolerate lumbar punctures well.

Phlebotomy, or a standard blood draw, is a common and safe procedure. Blood draws routinely gather information about various conditions, including non-small cell lung cancer. No major safety concerns have been reported when collecting genetic information from blood samples.

Overall, both lumbar puncture and phlebotomy are standard medical procedures with a good safety record. They are widely used for diagnosing and monitoring various medical conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential of using cerebral spinal fluid (CSF) and blood circulating tumor DNA for analyzing non-small cell lung cancer (NSCLC). Unlike traditional methods that rely heavily on tissue biopsies to study cancer, this approach uses a liquid biopsy technique. This method is less invasive and could provide real-time insights into the genetic makeup of the cancer, allowing for more personalized treatment strategies. By using ddPCR and the BC Cancer NGS panel on CSF and blood samples, researchers aim to uncover unique cancer markers that might lead to more targeted and effective therapies for NSCLC patients.

What evidence suggests that this trial's methods could be effective for analyzing molecular differences in NSCLC?

Research has shown that analyzing cerebrospinal fluid (CSF), the fluid around the brain and spine, can identify genetic changes in patients with non-small cell lung cancer (NSCLC). In this trial, participants will undergo a lumbar puncture to collect CSF, which may reveal key differences between cancer in the brain and other body parts. By comparing CSF to blood samples, researchers aim to identify specific gene changes not visible in regular blood tests. This method helps doctors select more precise treatments for cancer that has spread to the brain and spinal cord. Overall, evidence suggests that this approach could enhance the understanding and treatment of NSCLC. ^{6 7 8 9 10}

Who Is on the Research Team?

Cheryl Ho, MD

Principal Investigator

BC Cancer

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific lung cancer (EGFR mutant NSCLC) that has spread to the lining of the brain and spinal cord. They must be able to consent, have a life expectancy of at least 8 weeks, and their body should be functioning well enough for testing. People can't join if they have bleeding issues or conditions preventing safe lumbar puncture.

Inclusion Criteria

My lung cancer has a specific EGFR mutation and has spread.

Ability to give informed consent for the study procedures defined in this protocol.

Life expectancy of at least 8 weeks.

Exclusion Criteria

Subjects who are otherwise felt by the treating clinician to be unfit to proceed with this protocol.

I cannot have a lumbar puncture due to low platelets, bleeding issues, or cannot consent.

My MRI shows a condition in my spine that makes lumbar puncture unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline MRI brain and spine must be completed, and baseline quality of life questionnaires are collected

1-2 weeks

1 visit (in-person)

Molecular Testing

ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA

Ongoing

Every 12 weeks +/- 2 weeks

Follow-up

Participants are monitored for overall survival and quality of life, with assessments every 12 weeks

36 months

Every 12 weeks +/- 2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lumbar puncture and Phlebotomy

Trial Overview The study aims to find molecular differences between tumor DNA in cerebral spinal fluid (CSF) and blood in patients with leptomeningeal disease from lung cancer. It involves comparing CSF obtained by lumbar puncture with blood samples using advanced molecular tests.

How Is the Trial Designed?

Group I: Experimental arm Experimental Treatment 1 Intervention

ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Published Research Related to This Trial

In a study of 30 patients with advanced non-small-cell lung cancer (NSCLC), those diagnosed with cerebrospinal fluid (CSF) metastasis showed significantly higher frequencies of EGFR mutations (80%) and ALK fusions (50%) compared to a control group without CSF metastasis.

Patients with CSF metastasis had a median survival time of only 4.8 months, which is notably shorter than the 9.2 months median survival for those without CSF metastasis, indicating that gene mutations may not only increase the incidence of CSF metastasis but also worsen prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between cerebrospinal fluid metastasis and gene mutations in non-small-cell lung cancer patients. Ji, X., Du, Y., Liu, Y., et al.[2020]

Cerebrospinal fluid (CSF) from nonsmall cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) shows unique molecular features, indicating it could serve as a more effective liquid biopsy compared to plasma or primary tumor tissue.

In a study of 131 NSCLC patients, high somatic copy number variations (CNV) were found in CSF, and the presence of EGFR mutations was highly consistent across CSF, plasma, and tumor samples, suggesting CSF may provide reliable genetic information for treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis. Wang, Y., Jiang, F., Xia, R., et al.[2021]

In a study of 32 EGFR+ non-small cell lung cancer patients with leptomeningeal metastasis, switching to or initiating high-dose EGFR-tyrosine kinase inhibitors (TKIs) resulted in a significantly higher disease control rate (100% vs. 12.5%).

The overall survival for these patients was 27 months, but those with a worse clinical status after leptomeningeal metastasis had a median survival of only 4.2 months, highlighting the importance of treatment strategy and patient status in prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of molecular characteristics of cerebrospinal fluid for non-small cell lung cancer patients with leptomeningeal metastasis. Li, N., Liu, Y., Duan, J., et al.[2020]

In a study of 970 non-small cell lung cancer (NSCLC) patients with CNS metastases, cerebrospinal fluid (CSF) samples showed significantly higher rates of actionable mutations compared to plasma samples, particularly for copy number variants, indicating CSF's superior sensitivity for genomic profiling.

CSF analysis not only identified more mutations but also helped uncover resistance mechanisms to EGFR-targeted therapies in 78.87% of patients, suggesting its potential to guide more effective treatment strategies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic Alterations Identification and Resistance Mechanisms Exploration of NSCLC With Central Nervous System Metastases Using Liquid Biopsy of Cerebrospinal Fluid: A Real-World Study. Shen, F., Liang, N., Fan, Z., et al.[2022]

Cerebrospinal fluid (CSF) provides a more comprehensive view of genomic mutations in non-small cell lung cancer patients with leptomeningeal metastases compared to plasma, particularly for patients with single CNS progression, as shown by higher detection rates of key mutations like EGFR-amp.

Unique mutations associated with poor outcomes, such as CDKN2A/B and PIK3CA, were found exclusively in CSF samples, highlighting its potential as a valuable liquid biopsy medium for identifying prognostic markers in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid-derived circulating tumor DNA is more comprehensive than plasma in NSCLC patients with leptomeningeal metastases regardless of extracranial evolution. Yang, H., Wen, L., Zhao, C., et al.[2023]

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]

A study analyzing cerebrospinal fluid (CSF) from 46 patients with leptomeningeal metastases from non-small cell lung cancer (NSCLC) identified six potential biomarkers, including tyrosine and phenylalanine, which could help in diagnosing this condition.

The research utilized advanced metabolomic techniques and found that these biomarkers are linked to key metabolic pathways, such as glycolysis and amino acid metabolism, suggesting their role in the disease's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Untargeted metabolomics analysis of cerebrospinal fluid in patients with leptomeningeal metastases from non-small cell lung cancer. Li, H., Lin, Y., Zheng, S., et al.[2023]

The study analyzed 62 cerebrospinal fluid (CSF) specimens from 46 patients with suspected central nervous system metastases due to small-cell lung carcinoma, revealing a high consistency in cytologic diagnosis with an 87% agreement rate between observers.

Despite the high probability of malignancy in patients with meningeal carcinomatosis, 40% of those with confirmed cases were not diagnosed while alive, highlighting the challenges in accurately diagnosing malignancy through CSF cytology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid cytology diagnosis of meningeal carcinomatosis in patients with small-cell carcinoma of the lung. A study of interobserver and intraobserver variability. Pedersen, AG., Olsen, J., Nasiell, M.[2006]

Citations

1. withpower.com withpower.com/trial/phase-lung-neoplasms-3-2025-1793c

Lumbar Punctures for Lung Cancer · Info for Participants 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 ...

2. ctv.veeva.com ctv.veeva.com/study/lumbar-punctures-for-the-detection-of-ctdna-in-the-cerebrospinal-fluid-of-patients-with-stage-iii-an

Lumbar Punctures for the Detection of ctDNA in the ... Lumbar punctures for the collection of CSF may help doctors detect or measure changes in cell types, genes, and proteins of circulating tumor ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9475227/

Genotyping of cerebrospinal fluid in lung cancer patients with ... We performed a retrospective cohort study to assess the genetic profiles of paired CSF and plasma samples in lung cancer patients with LM.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/334899

CSF Analysis in EGFR Mutant Non-Small Cell Lung ... The aim of this pilot trial is to evaluate for molecular differences between cerebral spinal fluid (CSF) and blood circulating tumor DNA (ctDNA) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8628152/

A Systematic Review and Meta-analysis - PMC PTNB demonstrated an average tissue adequacy rate of 89.3% for molecular analysis in patients with NSCLC, with a complication rate of 17.3%. PTNB is a generally ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06816979

Study Details | NCT06816979 | Lumbar Punctures for the ... To prospectively confirm that cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) can be detected in patients diagnosed with metastatic non-small cell lung ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3306150/

Multidetector CT-Guided Lumbar Puncture in Patients with ... We conclude that MDCT-guided lumbar puncture is an effective and safe guiding modality for thecal sac access in patients with cancer.

8. news.cancerconnect.com news.cancerconnect.com/treatment-care/lumbar-puncture-is-used-to-diagnose-and-treat-certain-leukemias-and-cancers

Lumbar Puncture is Used to Diagnose and Treat Certain ... A lumbar puncture can help diagnose serious infections, such as meningitis or cancer involving the brain or spinal cord.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10728707/

Therapeutic role of EGFR - Tyrosine kinase inhibitors in non ... EGFR tyrosine kinase inhibitors (TKIs) exhibit potent anti-tumor activity and hold considerable promise for NSCLC patients with EGFR mutations.

10. lung.org lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/lung-cancer-staging/brain-metastasis

Brain Metastasis from Lung Cancer There are possible side effects of brain radiation, but it is generally considered safe. Your body does not become radioactive after treatment, ...