Actively Recruiting
Double-Dose Third-Generation EGFR-TKI Plus Bevacizumab and Intrathecal Chemotherapy for Refractory Leptomeningeal Metastatic NSCLC: A Phase II Study
Led by Second Affiliated Hospital of Nanchang University · Updated on 2026-04-23
30
Participants Needed
1
Research Sites
97 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
The goal of this clinical trial is to explore the efficacy and safety of double-dose third-generation EGFR-TKI combined with bevacizumab and intrathecal chemotherapy in treating advanced non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis that progressed after prior standard-dose third-generation EGFR-TKI treatment. It also aims to investigate the correlation between cerebrospinal fluid genetic characteristics and prognosis as well as subsequent efficacy prediction in patients with leptomeningeal metastasis after resistance to standard-dose third-generation EGFR-TKI. The main questions it intends to answer are: Does this combined treatment regimen improve leptomeningeal metastasis response rate (LM-ORR) evaluated by RANO-LM? What adverse events occur in patients during the treatment with this combined regimen? Researchers will conduct a single-arm phase II prospective study to assess the effectiveness and safety of the combined treatment, without a control group comparison. Participants will: Receive double-dose third-generation EGFR-TKI (osimertinib 160mg qd, furmonertinib 160mg qd, or almonertinib 220mg qd) + intrathecal pemetrexed (induction phase: 10mg twice a week for 4 weeks; maintenance phase: 10mg once a week for 4 weeks; consolidation phase: 30mg every 4 weeks until disease progression or intolerable toxicity) + bevacizumab 7.5mg/kg. Undergo screening assessments within 28 days before enrollment, including tumor imaging, laboratory tests, and cerebrospinal fluid examination. During the treatment period, conduct regular checkups and tests (such as blood routine, blood biochemistry, electrocardiogram, and imaging examinations) according to the protocol (once every 4 weeks in the first two treatment cycles, then once every 8 weeks). Complete quality of life assessment using the QLQ-C30 scale every 4 weeks and record changes in neurological symptoms and ECOG scores.
CONDITIONS
Official Title
Double-Dose Third-Generation EGFR-TKI Plus Bevacizumab and Intrathecal Chemotherapy for Refractory Leptomeningeal Metastatic NSCLC: A Phase II Study
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at the time of informed consent, any gender
- Histologically or cytologically confirmed advanced or metastatic NSCLC, stage IV
- Presence of EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation)
- Leptomeningeal metastasis progression after standard-dose first-, second-, or third-generation EGFR-TKI treatment
- ECOG performance status score of 0 or 1
- Adequate major organ function including hemoglobin 90 g/L, ANC 1.5 � 10^9/L, platelet count 100 � 10^9/L, WBC between 3.0 and 10.0 � 10^9/L, liver and kidney function within specified limits
- At least 21 days since last radiotherapy
- Expected survival of at least 3 months
- Ability to swallow oral medications or receive crushed medications via gastrostomy tube
- Agreement to use effective contraception during the study and for 3 months after last study drug administration (for both women and men)
- Voluntary participation with signed informed consent and willingness to comply with study procedures
You will not qualify if you...
- Major surgery within 4 weeks before starting treatment or planned major surgery during the study
- HIV infection or acquired immunodeficiency syndrome (AIDS)
- Active bacterial, fungal, or viral infections requiring intravenous antibiotics
- History of drug-induced pneumonitis, interstitial lung disease, or active pulmonary disease
- Severe cardiovascular events within 6 months before enrollment, including stroke, deep vein thrombosis, or pulmonary embolism
- Significant cardiovascular disease such as NYHA class II or higher heart failure, unstable angina, symptomatic arrhythmias, or prolonged QT interval >470 ms
- History of other systemic cancers within 5 years except certain cured cancers
- Use of strong CYP3A4 inducers
- Known severe allergy to study drugs or their components
- Pregnancy, breastfeeding, or refusal of effective contraception
- History of definite neurological or psychiatric disorders including epilepsy and dementia
- Any other condition deemed unsuitable for participation by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
Actively Recruiting
Research Team
J
jing cai Jing Cai
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here