Histologically Confirmed, Recurrent or Metastatic, Unresectable or Not Amenable to Radical Chemoradiotherapy Stage III or IV Non-Small Cell Lung Cancer (NSCLC)
Conditions
Interventions
Experimental group:Targeted Therapy plus Chemotherapy
Sponsors
Sichuan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age between 18 and 75 years old; 2. Willing to provide a handwritten consent form with the date; 3. Histologically confirmed, recurrent or metastatic non-small cell lung cancer (NSCLC) that is inoperable or not suitable for curative chemo-radiotherapy, stage III or IV; 4. A report from a top-tier hospital or qualified testing institution confirming NSCLC patients with an exon 21 L858R mutation and brain metastases; 5. According to RECIST 1.1, at least one measurable extracranial lesion, and at least one measurable intracranial lesion =5mm, with brain metastases not considered target lesions; 6. Patients with asymptomatic brain metastases, no more than 5 metastases, and no brainstem or meningeal involvement (meaning no neurological symptoms, no need for corticosteroids, no lesion larger than 1.5 cm, and no significant surrounding edema), or patients whose brain metastases are controlled or stable (controlled/stable brain metastases defined as having at least two imaging checks at least 4 weeks apart after treatment with no new or enlarged metastases, and steroids stopped 3 days before study drug administration; stable status must be confirmed before the first imaging in this study); 7. ECOG performance status 0-1, with an expected survival of at least 3 months; 8. Have not received systemic treatment for advanced NSCLC, including traditional Chinese medicine or patent Chinese medicine (for example, if anti-tumor Chinese medicine was used for no more than 7 days and stopped at least 2 weeks before the study drug treatment, participation is allowed); 9. Able to follow the required study procedures and take oral medication; 10. Have good organ function, including: (1) Good bone marrow function: hemoglobin >= 90 g/L, absolute neutrophil count (ANC) >= 1.5 × 10^9/L, platelets >= 80 × 10^9/L; (2) Good liver function: total bilirubin = 60 mL/min; (3) Heart function: assessed by Doppler ultrasound, left ventricular ejection fraction (LVEF) >= 50%; 11. Women and men of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose after signing the informed consent.
Exclusion criteria
Exclusion criteria: 1. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation; 2. Presence of EGFR T790M mutation, or unknown mutation status, or other mutation types; 3. Diagnosed with other malignant tumors in the past 5 years, or currently having other malignant tumors; 4. History of hemoptysis, hematochezia, or blood in sputum (or currently taking therapeutic anticoagulants for new thrombotic disease or having a bleeding tendency); 5. Tumor invading or near major blood vessels, with the main investigator assessing a risk of major bleeding; 6. Uncontrolled or severe systemic diseases including: (1) Uncontrolled hypertension (2) Fever above 38°C in the past week, or clinically significant active infections. Active pulmonary tuberculosis. Active fungal, bacterial, and/or viral infections requiring systemic treatment. (3) Clinically significant major abnormalities in resting ECG rhythm, conduction, or morphology, such as complete left bundle branch block, second-degree or higher cardiac conduction block, clinically significant ventricular arrhythmia or atrial fibrillation, unstable angina, congestive heart failure, chronic heart failure NYHA class >= 2. (4) Myocardial infarction, coronary/peripheral artery bypass, or cerebrovascular accident within 3 months. (5) 12-lead ECG QT interval (QTc) male >= 450 ms, female >= 470 ms. (6) Presence of risk factors leading to prolonged QT interval or increased risk of arrhythmia, such as heart failure, grade >=2 hypokalemia (according to CTCAE 4.03; grade 2 hypokalemia defined as serum K+ < lower limit of normal - 3.0 mmol/L with symptoms requiring treatment), congenital long QT syndrome, family history of long QT syndrome. (7) Using any medication known to prolong QT interval within 2 weeks before the first dose. (8) History of interstitial lung disease, drug-induced interstitial lung disease, interstitial pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease. 7. Using/consuming drugs or foods known to strongly inhibit CYP3A4 within 2 weeks, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice. 8. Using drugs known to strongly induce CYP3A4 within 2 weeks, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort. 9. Using drugs that are CYP3A4 substrates with a narrow therapeutic index within 2 weeks, including but not limited to dihydroergotamine, ergotamine, pimocaprin, astemizole, cisapride, and terfenadine. 10. Using strong P-gp inhibitors within 2 weeks, including but not limited to verapamil, cyclosporine A, and dexverapamil. 11. Patients who are positive for hepatitis C antibodies with HCV-RNA above normal, hepatitis B surface antigen positive with HBV-DNA above normal, cirrhosis patients, HIV antibody positive, or syphilis antibody positive. 12. Any gastrointestinal condition preventing oral medication intake, requiring IV nutrition, or previous surgery affecting drug absorption. 13. History of other diseases, metabolic dysfunction, or physical/lab results suggesting any condition that may prohibit study drug use, affect the interpretation of results, or put the patient at higher risk of treatment complications. 14. Subjects deemed by
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR);Overall Survival (OS);Intracranial Progression-Free Survival (iPFS);Safety and tolerability of lapatinib combined with bevacizumab and chemotherapy;Assessing the participant's quality of life (QoL); | — |
Countries
China
Contacts
Public ContactHang Zhou
Sichuan Cancer Hospital
Outcome results
None listed