Actively Recruiting
Efficacy and Safety of Double-Dose Third-Generation EGFR-TKI Combined With Bevacizumab and Intrathecal Chemotherapy in Advanced NSCLC Patients With Progressive Leptomeningeal Metastasis
Led by Second Affiliated Hospital of Nanchang University · Updated on 2026-04-23
30
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a combined treatment for advanced non-small cell lung cancer (NSCLC) patients who have leptomeningeal metastasis that worsened after standard-dose third-generation EGFR-TKI therapy. This Phase II study aims to assess the effectiveness and safety of a double-dose third-generation EGFR-TKI combined with bevacizumab and intrathecal chemotherapy. The study also explores how genetic features in cerebrospinal fluid relate to patient outcomes and predict treatment response after resistance to prior EGFR-TKI therapy. Participants will receive a combination of double-dose oral third-generation EGFR-TKI (osimertinib 160mg, furmonertinib 160mg, or almonertinib 220mg daily), intrathecal pemetrexed chemotherapy administered in induction, maintenance, and consolidation phases, and intravenous bevacizumab dosed at 7.5mg/kg. The treatment involves initial intensive phases followed by maintenance until disease progression or unacceptable side effects. All drugs are given according to specific schedules and dose adjustments are made based on tolerance and blood counts. Before starting treatment, participants undergo screening including imaging, lab tests, and cerebrospinal fluid exams. During treatment, regular monitoring includes blood tests, electrocardiograms, imaging assessments, and quality of life questionnaires every 4 to 8 weeks. Neurological symptoms and performance status are also tracked. Follow-up continues for safety and survival outcomes for about one year after treatment ends. The main measure is the response rate of leptomeningeal metastasis using RANO-LM criteria.
CONDITIONS
Brief 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...
- Aged 18 years or older at the time of consent
- Histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), stage IV
- Presence of EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation)
- Leptomeningeal metastasis progression after prior standard-dose first-, second-, or third-generation EGFR-TKI treatment
- ECOG performance status score of 0 or 1
- Adequate major organ function including specific blood counts and liver/kidney function within defined limits
- At least 21 days since last brain 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 and after study for women of childbearing potential 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 study treatment or planned during the study
- HIV infection or acquired immunodeficiency syndrome (AIDS)
- Active infections requiring intravenous antibiotic therapy
- History or evidence of drug-induced pneumonitis, interstitial lung disease, or significant active pulmonary disease
- Severe cardiovascular events within 6 months prior to enrollment
- Significant cardiovascular disease including NYHA class II or higher heart failure, unstable angina, symptomatic arrhythmias, or prolonged QTc interval
- History of other systemic malignant tumors within past 5 years except certain skin and cervical cancers
- Use of drugs or supplements that strongly induce CYP3A4
- Known severe allergy to study drugs or excipients
- Pregnancy, lactation, or refusal of contraception by patients of childbearing potential
- History of definite neurological or psychiatric disorders including epilepsy and dementia
- Other conditions deemed unsuitable for enrollment by the investigator
AI-Screening
AI-Powered Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for consent, medical history, imaging, laboratory tests, and assessments
Duration - Until disease progression or intolerable toxicity
Participants receive a combined treatment regimen including double-dose third-generation EGFR-TKI taken orally daily, intravenous bevacizumab, and intrathecal pemetrexed chemotherapy administered in induction, maintenance, and consolidation phases.
Multiple visits: twice weekly intrathecal chemotherapy for 4 weeks, then weekly for 4 weeks, then every 4 weeks; intravenous bevacizumab dosing as per protocol; assessments including physical exams, laboratory tests, electrocardiograms, and imaging every 2 to 8 weeks
Duration - Up to 1 year after treatment completion
Participants are monitored for safety and survival after the last study drug administration, including assessments of adverse events and disease status.
Safety follow-up visit 30 days after last treatment and survival follow-up visits every 3 months
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
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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