Diagnosis of Leptomeningeal Metastasis and the Monitoring of Intrathecal Chemotherapy Efficacy in NSCLC

NCT06346977 | Not Yet Recruiting

• 1 other identifier: DTO-20231214
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Diagnosis

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  From the date of intrathecal drug administration until the date of first documented disease progression or death due to any cause, whichever occurs first, with an assessment period up to a maximum of 36 months.

  up to a maximum of 36 months.

Secondary Outcomes (1)

• Overall survival (OS)

  up to a maximum of 36 months.

Study Arms (2)

LM group;

Leptomeningeal Metastasis Group

Drug: Pemetrexed

NLM group

Non-Leptomeningeal Metastasis Group

Interventions

Pemetrexed DRUG

Intrathecal injection of pemetrexed

LM group;

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

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union hospital

Wuhan, Hubei, 430000, China

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

In Part One of the study, plasma samples (1 mL) were collected from NLM group participants at the time of initial diagnosis, when they presented with no clinical symptoms or radiological evidence of meningeal metastasis. For LM group subjects, both plasma (1 mL) and cerebrospinal fluid (2 mL) were obtained within two weeks prior to receiving intrathecal chemotherapy. In Part Two, plasma and CSF were gathered from cohort subjects at three time points: within two weeks before intrathecal chemotherapy (baseline), at T0 (24 hours post-injection), and at T28 (28 days post-injection), with 1 mL of plasma and 2 mL of CSF collected at each instance. Plasma was acquired through venipuncture, while CSF was extracted via lumbar puncture. All collected samples were earmarked for proteomic analysis.

MeSH Terms

Conditions

Disease

Interventions

Pemetrexed

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Peng Ping, Dr.

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Ding, Dr.

CONTACT

02785726114; dingp1@hust.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor/Chief Physician

Study Record Dates

• First Submitted: March 27, 2024
• First Posted: April 4, 2024
• Study Start: April 1, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 4, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)