The Dynamic Monitoring of Cerebrospinal Fluid ctDNA

A Single-center Prospective Cohort Study to Explore the Efficacy and Prognosis of Dynamic Monitoring of Cerebrospinal Fluid ctDNA

Focusing on advanced EGFR mutation in NSCLC patients with leptomeningeal metastasis, vormetinib combined with OMMAYA lateral ventricle chemotherapy (pemetrexed) was used to dynamically monitor ctDNA in cerebrospinal fluid (CSF), analyze the ctDNA gene mutation profile of CSF in different patients, and explore the relationship between ctDNA and efficacy and prognosis.

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: pemetrexed

Detailed Description

This is a single-center prospective cohort study. Patients with advanced EGFR-mutated NSCLC with leptomeningeal metastasis were treated with vormetinib combined with OMMAYA lateral ventricle chemotherapy (pemetrexed). Dynamic monitoring of cerebrospinal fluid ctDNA was performed to analyze the ctDNA gene mutation profile of cerebrospinal fluid in different patients, and to explore the relationship between ctDNA and efficacy and prognosis. At the same time, the study of drug vacation in the treatment of leptomeningeal metastasis is to explore the efficacy and safety of brain drug vacation, so as to reduce the patient's tolerance to drugs and the side effects of drugs. The endpoint was progression-free survival (PFS) of intracranial lesions.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: fang S cun, M.D.; Phone Number: 025 83728558; Email: fang1984@aliyun.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 210029
      • Recruiting
      • Nanjing Brain Hospital
      • Contact: fang S cun, M.D.; Phone Number: 025 83728558; Email: fang1984@aliyun.com
      • Contact: fang S Cun; Phone Number: 83728558; Email: fang1984@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Advanced NSCLC patient with EGFR mutation, associated with leptomeningeal metastasis
• Patients who meet the requirements of OMMAYA cystlateral ventricle chemotherapy
• Age > 18 years
• Complete serologic tumor markers (CEA, SCC) and imaging data (enhanced CT and/or MRI, PET-CT)
• Liver, kidney, and hematologic measures were normal (as measured by laboratory testing within 1 week before enrollment in the absence of ongoing supportive care), with a neutrophil count of more than 1.5×109/L, a platelet count of more than 100×109/L, and a hemoglobin level of more than 9.0g/dl ，Bilirubin normal or <1.5×ULN; AST(SGOT), ALT(SGPT) <2.5×ULN; Serum creatinine <1.5×ULN
• The patients were fully aware of the study, provided voluntary written informed consent, and were able to adhere to the protocol-defined visit and follow-up procedures

Exclusion Criteria:

• Patients who do not meet the requirements of lateral ventricular chemotherapy
• History of allergy to vormetinib and pemetrexed
• Severe complications occurred during the treatment
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Severe infection in active stage or with poor clinical control
• Mentally ill, substance abusers and pregnant or lactating women
• No informed consent was signed
• Eligibility as judged by the other investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental group; Eligible patients with advanced non-small cell lung cancer with leptomeningeal metastasis were treated with vormetinib combined with OMMAYA lateral ventricle chemotherapy (pemetrexed).

Drug: pemetrexed; The efficacy of Furmonertinib combined with OMMAYA lateral ventricle chemotherapy (pemetrexed) was evaluated once a week during the treatment phase. After the brain lesions were evaluated as CR, the drug holiday study phase was added. During the study period, the patients were followed up once a week until the investigators deemed the subjects unfit to continue to participate in the study or the efficacy was evaluated as disease progression (PD).; Other Names: Furmonertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The progression-free survival time（PFS）	The time from the initiation of treatment to the observation of disease progression or death from any cause.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Occurrence and severity of AEs by NCI CTCAE v5.0	Up to 2 years

Collaborators and Investigators

• Sponsor: Jiangsu Province Nanjing Brain Hospital
• Investigators: Study Director: fang S cun, M.D., Nanjing Brain Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: MA-ENDO-202209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No