Table 4.

Ongoing clinical studies on CNS metastases including liquid biopsy

Study Number	Patient Population	Type of Study	Fluid Sample	Technique	Primary Outcome	Secondary Outcomes
NSCLC
NCT02607605	10 patients with advanced lung cancer with LM	Observational Prospective	CSF	Cell-free DNA (cfDNA) using QIAamp Circulating Nucleic Acid kit (Qiagen)	Positive rate between the cfDNA and cytological examination of CSF [time frame: 2 y]	The relationship between the number of cfDNA and OS [time frame: 2 y]
NCT02803619	60 patients with EGFRm+ NSCLC and LM	Observational Prospective	CSF	Not reported	OS after the diagnosis of leptomeningeal metastasis in NSCLC patients [time frame: 1 y]	---
NCT03029065	50 patients with BM or LM from NSCLC	Observational Prospective	CSF plasma	cfDNA using next- generation sequencing technique	Investigate whether the cfDNA can be used for concomitant diagnosis to improve the treatment efficacy and prognosis of patients with brain (meningeal) metastasis by monitoring tumor-related genetic mutations in cfDNA in the plasma and CSF [time frame: 6 mo]	---
NCT03257735	50 patients with BM from NSCLC	Observational Prospective	CSF plasma tumor tissue	cfDNA using next- generation sequencing technique	To compare the gene mutation in CSF, blood, and tumor tissue at baseline and after 2 months of treatment [time frame: 2 mo]	To compare the gene mutation status of CSF, blood, and tumor tissue after the first session and at the time of tumor progression [time frame: 6 mo]
NCT03257124	80 patients with EGFR T790M mutated NSCLC and BM and/ or LM who failed tyrosine kinase Inhibitors	Phase II trial experimental arm: AZD9291 (160 mg per oral daily; 1 cycle of 28 days) in BM or LM cohort in T790M positive	CSF plasma tumor tissue	Not reported	OS in BM and LM cohorts, respectively	- Whole body disease control rate - Time to brain progression - PFS - Adverse events (CTCAE v4.0) - Exploratory analysis of EGFR mutation/T790M in tissue, plasma, and CSF
Breast cancer
NCT03252912	51 patients with LM from breast cancer	Observational Prospective	Plasma	CTCs using CellSearch technique	Sensitivity of the CellSearch technique on CSF samples in comparison with the conventional cytology on 1‒3 CSF samples [time frame: through study completion, an average of 2 y]	—
NCT01645839	144 patients with LM from breast cancer	Phase III trial • Arm A: Standard systemic treatment without intrathecal liposomal ARA-C • Arm B: Standard systemic treatment with intrathecal liposomal ARA-C	CSF	CTCs using Veridex technique	Neurological PFS	- Clinical PFS (Montreal Cognitive Assessment Scale [MOCA] score) - Cytological PFS - Radiological PFS - OS - Tolerability of liposomal ARA-C - Research and quantification of tumor cells in the CSF for the diagnosis and monitoring of meningeal metastasis of breast cancer
Miscellanea
NCT02071056	22 patients with LM from metastatic solid tumors	Observational Prospective	CSF plasma tumor tissue	Not reported	Tumor DNA detectability and cytological confirmation of leptomeningeal metastasis [time frame: 1 y]	- Comparison of circulating tumor DNA levels in CSF with levels in plasma. - Correlation of circulating tumor DNA levels and patient survival. - Circulating tumor DNA detection in CSF of patients with cytological evidence of leptomeningeal metastasis. - Circulating tumor DNA identification in the CSF of patients prior to diagnosis of leptomeningeal metastasis. - Measurement of circulating tumor DNA levels and cancer cell numbers in CSF following initiation of intrathecal chemotherapy for leptomeningeal metastasis.   [time frame: 1 y]
NCT01713699	100 patients with LM from metastatic solid tumors	Observational Prospective	CSF	CTCs EpCAM + detected by CellSearch technique	To determine the sensitivity and specificity of detection of CTCs in patients with EpCAM expressing tumors compared with cytology in the CSF of patients clinically suspected for LM [time frame: 3 mo after end of study]	- To determine the relationship between the number of CTCs in CSF and the patient’s neurological condition and World Health Organization performance score - To determine the change in the CTC number between two sampling points and correlate this with the patient’s neurological condition and therapy - To determine the relationships between demographics/tumor status and CTCs number in CSF. - To determine the relationship between the CTC cells in the CSF and the CTCs in the peripheral blood - To confirm EPCAM positivity in archived primary tumor tissue and tumor cells in CSF. -  To compare the predictive value of 2 CTC enumeration methods   [time frame: 3 mo after end of study]