ctDNA-driven Adaptive Proton Craniospinal Irradiation in Non-Small Cell Lung Cancer With Leptomeningeal Metastasis After Resistance to Third-Generation TKIs in the Consolidation Phase
This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.
About the trial
\*\*Brief Summary (English)\*\* The goal of this clinical trial is to learn if a risk-adaptive consolidation therapy, guided by cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) clearance kinetics after induction intrathecal pemetrexed, can improve intracranial progression-free survival (iPFS) compared to standard intrathecal pemetrexed consolidation in patients with leptomeningeal metastasis (LM) from EGFR-mutant non-small cell lung cancer (NSCLC) that has progressed on third-generation EGFR-TKIs. It will also learn about the safety and tolerability of proton craniospinal irradiation (pCSI) in this setting. The main questions it aims to answer are: * Does risk-adaptive consolidation therapy (pCSI with or without concurrent low-dose intrathecal pemetrexed) prolong iPFS compared to standard intrathecal pemetrexed consolidation? * What medical problems do participants have when receiving pCSI or intrathecal pemetrexed? Researchers will compare the experimental arm (risk-adaptive consolidation: pCSI for intermediate-risk, or pCSI with concurrent low-dose intrathecal pemetrexed for high-risk patients) to the control arm (standard intrathecal pemetrexed consolidation) to see if the adaptive strategy improves survival outcomes. Participants will: * Receive induction intrathecal pemetrexed (40 mg, biw, q3w for 2 cycles) via Ommaya reservoir. * Undergo CSF collection at baseline and after induction for ctDNA (maxVAF) analysis to determine risk stratification (low, intermediate, high). * If stratified as intermediate or high risk, be randomly assigned to either standard intrathecal pemetrexed consolidation or risk-adaptive consolidation (pCSI 30 GyE/10f for intermediate-risk; pCSI 30 GyE/10f with concurrent intrathecal pemetrexed 30 mg on d1, d8 for high-risk). * Receive maintenance intrathecal pemetrexed (40 mg, q4w) until intracranial progression. * Undergo regular efficacy assessments (contrast-enhanced MRI of brain and whole spine) every 8 weeks, and complete neurocognitive and quality-of-life questionnaires.
Original English text from ClinicalTrials.gov
Who can (and can't) join
✓ Qualifies
- •Wiek 18-75 lat i wyrażenie pisemnej zgody na udział w badaniu
- •Potwierdzony rak płuca (nie-drobnokomórkowy) z mutacją EGFR
- •Przerzuty do opon mózgowych (błon otaczających mózg i rdzeń) potwierdzone badaniem płynu lub obrazowaniem
- •Pogorszenie choroby mimo leczenia nowoczesnymi lekami celowanymi (osimertinib, almonertinib lub furmonertinib)
- •Posiadanie zbiornika Ommaya (urządzenie do podawania leków do płynu mózgowo-rdzeniowego)
- •Stabilna choroba poza mózgiem i rdzeniem
- •Ogólny stan zdrowia pozwalający tolerować leczenie (wynik Karnofsky'ego co najmniej 70)
- •Oczekiwana przeżywalność co najmniej 3 miesiące
Simplified criteria — AI translation
Trial details
- Minimum age
- 18 Years
- Maximum age
- 75 Years
- Last updated (source)
- August 7, 2026
- Sex
- No restrictions
Therapies / drugs in trial
Locations (3)
Anhui Provincial Cancer Hospital
Hefei, China
The First Affiliated Hospital of USTC Anhui Provincial Hospital
Hefei, China
Nanjing Brian Hospital
Nanjing, China
Trial contact
ShangHu Yuan, MD
Contact information from ClinicalTrials.gov. Contact in English.
Share this trial
Data from ClinicalTrials.gov. AI-assisted translation, last sync: 8/8/2026.
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