Brain metastasis tumor
Conditions
Interventions
Group 1:Vebreltinib 100mg twice daily (BID) + Osimertinib 80mg once daily (QD) + Gamma Knife
Group 2:Vebreltinib 150mg twice daily (BID) + Osimertinib 80mg once daily (QD) + Gamma Knife
Group 3:Vebreltinib 200mg twice daily (BID) + Osimertinib 80mg once daily (QD) + Gamma Knife
Sponsors
Beijing Tiantan Hospital Affiliated to Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be enrolled in this trial: 1.Voluntarily signed a written informed consent form to participate in the study; willing and able to comply with study-related visits and procedures; 2.Male or female aged 18 years or older; 3.Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC); classified as stage IIIB-IV according to the AJCC 8th edition lung cancer staging system (external pathological reports are acceptable); 4.Development of new intracranial metastases or progression of original intracranial metastatic lesions during monotherapy with osimertinib, without changes to the antitumor treatment regimen; 5.Enhanced MRI confirms at least one intracranial metastatic lesion measurable according to RANO-BM criteria (lesions previously treated with radiotherapy cannot be considered target lesions unless clear progression occurs after radiotherapy); 6.Karnofsky Performance Status (KPS) score >= 70; 7.Intracranial tumor tissue biopsy pathologically confirmed to have one of the following MET abnormalities: MET exon 14 skipping mutation (MET14 skip), MET gene amplification, MET gene fusion, or MET protein overexpression. MET14 skip mutation: acceptable detection results from local laboratories using RT-qPCR, DNA next-generation sequencing (NGS), or RNA NGS. MET gene amplification: acceptable detection results from local laboratories using FISH/NGS on tumor tissue or liquid biopsy (GCN >= 5, GCN/CEP7 >= 2). MET gene fusion: acceptable detection of ZM fusion gene positivity from local laboratories; MET protein overexpression: acceptable immunohistochemistry (IHC) results from local laboratories with an H-Score >= 200; 8.Clinically assessable for gamma knife treatment: = 1.5×10^9/L; 2) Hemoglobin >= 90 g/L; 3) Platelets >= 75×10^9/L; 4) Serum total bilirubin 50 mL/min, calculated using the Cockcroft-Gault formula: (140 - age [yr]) × weight (kg) × 1.23 × (0.85 if female) / serum creatinine (µmol/L); 8) Men and women of childbearing potential must agree to use effective contraception from the time of signing the informed consent until 3 months after the last dose of study drug. Women of childbearing potential must have a negative serum pregnancy test within =7 days before the first study drug administration.
Exclusion criteria
Exclusion criteria: 1. Prior treatment history including any of the following: 1) Major surgery (e.g., thoracic, abdominal, or pelvic surgery) within 4 weeks before enrollment, or brain metastasis resection within 2 weeks, or failure to recover from surgical side effects. Thoracoscopic biopsy and mediastinoscopy are not considered major surgery, and patients may enroll 1 week after such procedures; 2) Prior brain radiotherapy before study treatment initiation, chest radiotherapy to the lung field 470 ms on three consecutive electrocardiograms (ECGs) obtained at least 5 minutes apart (preferably within 1 hour) during screening, with an average QTcF >470 ms calculated using Fridericia’s formula; 2)Significant cardiac arrhythmias (e.g., complete left bundle branch block, second or third-degree heart block, ventricular arrhythmia), uncontrolled supraventricular or nodal arrhythmias, or other uncontrolled cardiac arrhythmias; 3) Risk factors for prolonged QTc interval, such as uncorrectable chronic hypokalemia, hereditary long QT syndrome, or use of QT-prolonging medications; 4) New York Heart Association (NYHA) class >=3 congestive heart failure; 5) Unstable or uncontrolled cardiac conditions (e.g., unstable angina, uncontrolled hypertension defined as diastolic blood pressure >100 mmHg and/or systolic blood pressure >160 mmHg regardless of antihypertensive use; initiation or adjustment of antihypertensive therapy before screening is permitted); 9. Radiological or cerebrospinal fluid pathological confirmation of spinal cord, meninges, or leptomeningeal tumor metastases; history of brain tumor or stroke (hemorrhagic or ischemic); 10. Significant ocular abnormalities, particularly severe dry eye syndrome, keratoconjunctivitis sicca, severe exposure keratitis, or other conditions increasing the risk of epithelial damage; 11. Diagnosis of another primary malignant disease within the past 3 years requiring treatment, except for completely resected basal cell carcinoma, squamous cell ski
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events;physical examination;Vital signs;12-lead electrocardiogram;Echocardiogram;laboratory tests; | — |
Secondary
| Measure | Time frame |
|---|---|
| intracranial progression-free survival (iPFS);progression-free survival (PFS);intracranial objective response rate (iORR);intracranial disease control rate (iDCR);overall survival (OS); | — |
Countries
China
Contacts
Public ContactBao Zhaoshi
Beijing Tiantan Hospital Affiliated to Capital Medical University
Outcome results
None listed