High-dose firmonertinib plus chemotherapy injected into the spinal fluid for EGFR-mutant NSCLC with leptomeningeal spread

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

Patients with stage IV EGFR-mutant NSCLC and confirmed leptomeningeal metastases will receive oral high-dose firmonertinib together with intrathecal pemetrexed at a single center. Treatment response and safety will be tracked prospectively with clinical exams, imaging, and regular cerebrospinal fluid (CSF) sampling. Investigators will use CSF cell-free DNA (cfDNA) to monitor tumor genetic changes and early treatment response in addition to standard neurologic and survival outcomes. The protocol is a Phase 4 interventional approach aimed at measuring tolerability and potential clinical benefit compared with historical outcomes.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Obtain an informed consent form signed by the patient or their legal representative;
* Age greater than or equal to 18 years old;
* According to the 9th edition TNM staging of lung cancer by the International Association for the Study of Lung Cancer and the Joint Committee on Cancer Staging in the United States, metastatic (stage IV) NSCLC with histological or cytological confirmation;
* Confirmed by histological or cytological specimens tested in the central laboratory to have EGFR exon 19 deletion mutation (19DEL) or exon 21 L858R point mutation (L858R), which can exist alone or in combination;
* ECOG physical condition score is 0-3 points, with an expected life expectancy of ≥ 12 weeks;
* According to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1), there should be at least one measurable lesion;
* According to the "EANO-ESMO" diagnostic criteria for meningeal metastasis (Type I: positive cerebrospinal fluid cytology or biopsy; Type II: limited to typical clinical symptoms and neuroimaging findings), for clinical judgment. Patients with leptomeningeal metastases who can be included in the study are type I patients and type II patients with EGFR mutations in cerebrospinal fluid ctDNA; merged brain parenchymal metastases can also be included in the study;
* Progress in first-line treatment with first and second-generation EGFR-TKI;
* Progress in first-line conventional dose treatment with third-generation EGFR-TKI;
* The subject must accept and be able to cooperate with the lumbar puncture procedure, and confirm that there are no contraindications to chemotherapy or lumbar puncture;
* At least 4 weeks before treatment, all extracranial symptoms must be stable, and there must be no CNS complications requiring emergency neurosurgical intervention.

Exclusion Criteria:

* Squamous cell carcinoma of the lung;
* Known history of hypersensitivity reactions to drugs with or without active excipients or similar structures or categories to the investigational drug for famotinib/pemetrexed;
* Confirmed EGFR exon 20 insertion mutation;
* At the beginning of drug treatment, if the toxicity associated with previous anti-tumor therapy has not recovered to ≤ CTCAE Grade 1, except for peripheral neurotoxicity caused by hair loss or chemotherapy ≤ CTCAE Grade 2;
* Excluding skin basal cell carcinoma, cervical carcinoma in situ, and ductal carcinoma of the breast that have been effectively controlled and have been diagnosed with other malignant tumors or have a history of other malignant tumors in the past 5 years;
* Patients who are deemed ineligible by researchers to participate in this study, such as those who are highly likely to be unable to comply with the study protocol, constraints, and requirements, or other situations determined by the researcher at their discretion;
* Pregnancy or lactation.

Where it's running

• Wuhan Union Hospital
  Wuhan, Hubei, China Recruiting

Study contacts

• Principal investigator: Xiaorong Dong, Dr — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: Peng Ding, Dr
• Email: dingp1@hust.edu.cn
• Phone: 02785726114

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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.