cfDNA methylome profiling for detection and subtyping of small cell lung cancers.
Francesca Chemi, Simon P Pearce, Alexandra Clipson...
https://pubmed.ncbi.nlm.nih.gov/35941262Actively Recruiting
Phase 4
Age: 18Years +
All Genders
ID07092202
Exploratory Study of High-Dose Firmonertinib Combined With Intrathecal Pemetrexed for EGFR Mutant NSCLC with Leptomeningeal Metastases Using cfDNA Monitoring
Led by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Updated on 2025-07-29
40
Participants Needed
1
Research Sites
26 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Leptomeningeal metastases (LM) are a rare but serious form of spread in advanced non-small cell lung cancer (NSCLC), often linked to EGFR mutations and associated with a poor outlook. Researchers aim to evaluate whether high-dose Firmonertinib combined with intrathecal chemotherapy can improve treatment outcomes for patients with EGFR mutant NSCLC who develop LM. This study also explores the potential of cerebrospinal fluid (CSF) circulating free DNA (cfDNA) as a biomarker to monitor treatment response in LM, addressing the current lack of effective monitoring tools. Participants will receive Firmonertinib at 160 mg orally once daily along with intrathecal injections of pemetrexed. The dosage of pemetrexed depends on body weight: for those above 50 kg, an induction phase with 40 mg on days 1 and 5 every 3 weeks for 4 cycles followed by consolidation with 40 mg every 4 weeks until CSF ctDNA is negative; for those below 50 kg, similar schedules apply with 30 mg doses. This prospective, multicenter, single-arm trial assesses the safety and efficacy of this combined high-dose targeted and local chemotherapy approach. During the study, participants will undergo dynamic monitoring of cfDNA levels in both cerebrospinal fluid and peripheral blood to evaluate treatment effects and safety. The primary outcome is progression-free survival over 2 years. Patients will have regular assessments including laboratory tests and lumbar punctures for CSF collection, and their physical condition will be monitored to ensure adherence and manage side effects. The study spans from April 2025 to November 2027, providing comprehensive follow-up for efficacy and biomarker validation.
CONDITIONS
Brief Title
Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Signed informed consent from patient or legal representative
- Age 18 years or older
- Confirmed metastatic (stage IV) NSCLC by histology or cytology
- EGFR exon 19 deletion or exon 21 L858R mutation confirmed by central lab
- ECOG performance status 0-3 with expected survival ≥ 12 weeks
- At least one measurable lesion per RECIST 1.1 criteria
- Diagnosed leptomeningeal metastases type I or type II with EGFR mutation in CSF ctDNA
- Progression after first-line treatment with first/second-generation EGFR-TKI
- Progression after first-line conventional dose third-generation EGFR-TKI
- Ability and willingness to undergo lumbar puncture and intrathecal chemotherapy
- Stable extracranial symptoms for at least 4 weeks before treatment without urgent CNS intervention
You will not qualify if you...
- Squamous cell carcinoma of the lung
- Known hypersensitivity to famotinib, pemetrexed, or similar drugs
- Confirmed EGFR exon 20 insertion mutation
- Toxicity from prior anti-tumor therapy not recovered to CTCAE Grade 1, except specified exceptions
- Other malignant tumors or history of malignancy within 5 years, except certain controlled cancers
- Deemed unable to comply with study protocol or requirements
- Pregnancy or lactation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
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3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Treatment
Duration - Induction period: approximately 12 weeks; Consolidation period: varies until cerebrospinal fluid ctDNA is negative
Participants receive high-dose Firmonertinib daily and intrathecal injections of pemetrexed according to weight-based dosing schedules during induction and consolidation periods to treat EGFR mutant NSCLC with leptomeningeal metastases.
Intrathecal injections on Day 1 and Day 5 of each 3-week cycle for 4 cycles during induction, then injections every 4 weeks during consolidation
Trial Site Locations
Total: 1 location
1
Wuhan Union Hospital
Wuhan, Hubei, China, 430022
Actively Recruiting
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Research Team
P
Peng Ding, Dr
X
Xiaorong Dong, Dr
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
Whole brain radiation therapy does not improve the overall survival of EGFR-mutant NSCLC patients with leptomeningeal metastasis.
Weiwei Yan, Yang Liu, Ji Li...
https://pubmed.ncbi.nlm.nih.gov/31521171Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+ NSCLC: an expanded, single-arm, phase II clinical trial.
C Fan, Z Jiang, C Teng...
https://pubmed.ncbi.nlm.nih.gov/38377785Efficacy and Safety of Intrathecal Pemetrexed Combined With Dexamethasone for Treating Tyrosine Kinase Inhibitor-Failed Leptomeningeal Metastases From EGFR-Mutant NSCLC-a Prospective, Open-Label, Single-Arm Phase 1/2 Clinical Trial (Unique Identifier: ChiCTR1800016615).
Chengjuan Fan, Qiuyu Zhao, Li Li...
https://pubmed.ncbi.nlm.nih.gov/33989780Efficacy and safety of re-challenging 160 mg furmonertinib for advanced NSCLC after resistance to third-generation EGFR-TKIs targeted agents: A real-world study.
Rongbin Qi, Xinyu Fu, Yingying Yu...
https://pubmed.ncbi.nlm.nih.gov/37604026Successful salvage therapy using high-dose furmonertinib (AST2818) for non-small-cell lung cancer after Osimertinib resistance: a case report.
Daoan Cheng, Shuxian Tang, Dong Li...
https://pubmed.ncbi.nlm.nih.gov/35946524Intracranial efficacy and safety of furmonertinib 160 mg with or without anti-angiogenic agent in advanced NSCLC patients with BM/LM as salvage therapy.
Ziyi Xu, Xuezhi Hao, Qi Wang...
https://pubmed.ncbi.nlm.nih.gov/36870951Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study.
Yuankai Shi, Xingsheng Hu, Shucai Zhang...
https://pubmed.ncbi.nlm.nih.gov/33780662Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study.
James C H Yang, Sang-We Kim, Dong-Wan Kim...
https://pubmed.ncbi.nlm.nih.gov/31809241Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status.
Jiyun Lee, Yoon La Choi, Joungho Han...
https://pubmed.ncbi.nlm.nih.gov/32652216