Double-dose third-generation EGFR-TKI with bevacizumab and intrathecal chemotherapy for leptomeningeal NSCLC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a prospective, single-arm Phase II study testing a combined regimen of double-dose third-generation EGFR-TKI, bevacizumab, and intrathecal chemotherapy in patients with EGFR-mutant advanced NSCLC who have leptomeningeal progression after prior standard-dose third-generation EGFR-TKI. The primary efficacy measure is leptomeningeal objective response rate (LM-ORR) evaluated by RANO-LM, with safety and adverse events systematically recorded. The study will also collect cerebrospinal fluid for genetic analysis to explore associations between CSF mutations and prognosis or subsequent treatment response. Participants must be adults with confirmed EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R), ECOG 0-1, and adequate organ function, and all treatments and intrathecal administrations are given at the lead site.

Why it matters

Who can join: the full rules

Inclusion Criteria

* Aged ≥ 18 years at the time of signing the informed consent form, regardless of gender.
* Histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), staged as IV according to the 8th edition of the IASLC TNM classification (2015).
* Presence of EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation).
* Leptomeningeal metastasis (LM) progression after standard-dose first-, second-, or third-generation EGFR-TKI treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Adequate major organ function, defined as: hemoglobin (Hb) ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count (PLT) ≥ 100 × 10\^9/L, white blood cell count (WBC) ≥ 3.0 × 10\^9/L and ≤ 10.0 × 10\^9/L; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; creatinine clearance ≥ 50 ml/min (for patients with liver metastases, TBIL ≤ 3.0 × ULN, ALT and AST ≤ 5.0 × ULN); activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) ≤ 1.5 × ULN.
* At least 21 days since the last radiotherapy (including whole-brain radiotherapy or local radiotherapy for brain metastases).
* Expected survival ≥ 3 months.
* Ability to swallow oral medications (or receive crushed medications via gastrostomy tube if unable to swallow).
* For women: Agreement to use effective contraception (e.g., surgical sterilization or protocol contraception) within 14 days prior to enrollment, during the study, and for 3 months after the last study drug administration.
* For men: Agreement to use effective contraception (e.g., surgical sterilization or protocol contraception) during the study and for 3 months after the last study drug administration.
* Voluntary participation, signed informed consent, and willingness to comply with study procedures and protocols.

Exclusion Criteria

* Major surgery within 4 weeks prior to the start of study treatment, or need for major surgery during the study.
* Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
* Active bacterial/fungal/viral infections requiring intravenous antibiotic therapy.
* Drug-induced pneumonitis or interstitial lung disease, or evidence of clinically significant active pulmonary disease.
* Severe cardiovascular events within 6 months prior to enrollment, including cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.
* Significant cardiovascular disease, such as New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, symptomatic arrhythmias requiring treatment, or corrected QT interval (QTcF) \> 470 ms on consecutive electrocardiograms.
* History of other systemic malignant tumors within the past 5 years (except for cured basal cell carcinoma, carcinoma in situ of the cervix, and ovarian cancer).
* Use of drugs or supplements known to be strong inducers of CYP3A4.
* Known severe allergy to any study drug or its excipients.
* Pregnancy, lactation, or refusal of effective 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.

Where it's running

• The Second Affiliated Hospital of Nanchang University
  Nanchang, Jiangxi, China Recruiting

Study contacts

• Study coordinator: jing cai Jing Cai
• Email: cjdl879@163.com
• Phone: 15270905381

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.