Clinical trial NCT06346977: Diagnosis of Leptomeningeal Metastasis and the Monitoring of Intrathecal Chemotherapy Efficacy in NSCLC
Official title: A Prospective Study on the Diagnosis of Leptomeningeal Metastasis and the Monitoring of Intrathecal Chemotherapy Efficacy in NSCLC Based on Proteomics
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Diagnosis
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2024-04-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC), are staged as IV according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.

Brief summary: Non-small cell lung cancer (NSCLC), occupying a disquieting position as the second most prevalent and deadliest neoplasm worldwide, afflicts an estimated 30% of its patients with intracranial metastatic spread. Among these, leptomeningeal metastasis (LM) is an exceptionally surreptitious and perilous manifestation, often evading timely and accurate diagnosis. The clinical landscape is further complicated by the presence of patients who, due to various reasons, are unable to undergo lumbar puncture, a procedure crucial for the investigation of LM. Moreover, even when cerebrospinal fluid (CSF) analysis via conventional cytological and immunohistochemical methods is attempted, a definitive diagnosis of LM may remain elusive in a subset of cases.

Intrathecal chemotherapy, particularly via the administration of pemetrexed, which has demonstrated both notable efficacy and an acceptable safety profile when delivered directly into the cerebrospinal space, constitutes a cornerstone of treatment for NSCLC-LM. Despite its importance, the lack of robust, validated biomarkers to gauge the therapeutic response to such interventions represents a significant knowledge gap. This deficit is compounded by the inherent challenges associated with CSF samples, including their limited availability and the suboptimal sensitivity and high resource demands of current ctDNA assessment techniques.

To address these pressing diagnostic and monitoring needs in NSCLC-LM management, the investigator proposes a forward-looking, non-interventional clinical study harnessing the power of cutting-edge proteomic technologies. These platforms, characterized by their high throughput, exquisite sensitivity, and minimal sample volume requirements, offer a promising avenue for elucidating the intricacies of chemotherapy response in intrathecal therapy. The study aims to provide valuable insights into improving diagnostic accuracy for LM in NSCLC patients and to establish a more rigorous framework for assessing treatment efficacy in individuals undergoing intrathecal chemotherapy, ultimately contributing to enhanced patient care and personalized therapeutic strategies.

Detailed description: The research is structured into two distinct phases. In the inaugural segment, the investigator plans to assemble a comprehensive dataset by procuring plasma or cerebrospinal fluid (CSF) samples from 30 individuals presenting with confirmed CSF positivity for LM, juxtaposed against an equal number of advanced NSCLC cases manifesting neither clinical signs nor radiographic indicators of meningeal involvement. These biological materials will be subjected to rigorous proteomic interrogation, with the overarching goal of discerning distinctive proteomic signatures that can accurately discriminate between NSCLC patients with and without LM.

In the subsequent phase, the study's focus shifts to therapeutic response monitoring. Maintaining the same cohort of CSF-positive NSCLC-LM patients initially recruited in Phase One, the researcher will systematically collect plasma and CSF samples at critical junctures during their treatment trajectory: specifically, within the two-week period preceding intrathecal chemotherapy initiation (establishing a baseline), immediately following the intervention at T0 (24 hours post-administration), and at the T28 milestone (28 days post-injection). Simultaneously, meticulous documentation of each patient's treatment response, disease progression dynamics, and overall survival metrics will be meticulously compiled. This concerted effort is designed to harness the power of proteomics in providing a real-time, molecular snapshot of chemotherapy effectiveness, thereby offering invaluable insights into the therapeutic efficacy of intrathecal chemotherapy in the context of NSCLC-LM management.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Histologically or cytologically confirmed diagnosis of NSCLC, stage IV according to the 8th edition of the International Association for the Study of Lung Cancer (IASLC) TNM Staging Manual
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2
* At least one lesion meeting the target lesion (TL) criteria of RECIST 1.1 at baseline. Must have imaging documentation of pretreatment tumor assessment by CT or MRI scan performed within 28 days before treatment initiation
* No prior intrathecal chemotherapy

Exclusion Criteria:

* History of allogeneic organ transplantation
* Active or documented history of autoimmune or inflammatory disorders (including inflammatory bowel disease \[such as colitis or Crohn's disease\], diverticulitis \[except diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener's syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, pituitary itis, uveitis, etc.\])
* Active history of primary immunodeficiency
* History of another malignancy within the past 3 years

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: up to a maximum of 36 months.
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: up to a maximum of 36 months.
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union hospital
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Peng Ping, Dr.
role: PRINCIPAL_INVESTIGATOR
References: