OncoMatch/Clinical Trials/NCT07751536
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
Is NCT07751536 recruiting? Yes, currently enrolling (Sep 2026). This NA trial studies Intrathecal pemetrexed for leptomeningeal metastasis from lung cancer.
Treatment: Intrathecal pemetrexed — \*\*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.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Other
Cancer type
Non-Small Cell Lung Carcinoma
Biomarker criteria
Required: EGFR sensitizing mutation
harbouring EGFR-sensitive mutations (including 19del and exon 21 L858R)
Required: EGFR exon 19 deletion
harbouring EGFR-sensitive mutations (including 19del and exon 21 L858R)
Required: EGFR l858r
harbouring EGFR-sensitive mutations (including 19del and exon 21 L858R)
Disease stage
Metastatic disease required
Leptomeningeal metastasis (LM) diagnosed according to the EANO-ESMO guidelines
Demographics
Prior therapy
Must have received: third-generation EGFR tyrosine kinase inhibitor (osimertinib, almonertinib, furmonertinib)
Disease progression of LM documented after treatment with third-generation EGFR-TKIs (including osimertinib, almonertinib, or furmonertinib)
Cannot have received: whole-brain radiotherapy
Patients who have previously received whole-brain radiotherapy
Cannot have received: photon radiotherapy to involved fields of the brain and spinal cord
Patients who have previously received ... photon radiotherapy to involved fields of the brain and spinal cord
Lab requirements
Blood counts
Haemoglobin (Hb) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelets (PLT) ≥ 75 × 10⁹/L
Kidney function
Serum Creatinine (Cr) ≤ 1.5 × ULN or Calculated Creatinine Clearance (CrCl) ≥ 50 mL/min (Cockcroft-Gault formula)
Liver function
Total Bilirubin (TBIL) ≤ 2.0 × ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome); ALT and AST ≤ 5.0 × ULN
Adequate organ and bone marrow function as defined below (within 14 days prior to initiation of study treatment)...
Structured fields extracted by AI. May contain errors — verify against the official protocol.
Frequently asked questions
Is NCT07751536 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior whole-brain radiotherapy, photon radiotherapy to involved fields of the brain and spinal cord disqualifies patients from enrollment.
Does this trial require EGFR?
Yes, EGFR sensitizing mutation is a required biomarker for enrollment.
Does this trial require EGFR?
Yes, EGFR exon 19 deletion is a required biomarker for enrollment.
Does this trial require EGFR?
Yes, EGFR l858r is a required biomarker for enrollment.
Is there an age limit?
Yes. Patients must be 75 years or younger.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualifyRelated pages