lung cancer
Conditions
Interventions
Experimental:Osimertinib alone
Active Comparator:Osimertinib combined with pleurodesis
Sponsors
Shanghai Chest hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be able to understand and comply with the requirements of the trial protocol; 2. Male or female aged 18 to 80 years old; 3. Patients with advanced non-small cell lung cancer (stage IV) with EGFR activation mutations (including EGFR19del deletion or L858R); 4. Malignant pleural effusion was confirmed by finding malignant cells in pleural effusion; 5. Massive malignant pleural effusion should meet one of the following conditions: (1) B-ultrasound showed that the depth of pleural fluid perfusion was more than 50 mm; (2) Computed tomography (CT) showed that the depth of pleural fluid perfusion was more than 50 mm; (3) X-ray images showed that the depth of pleural fluid perfusion was more than half of that of one side of the chest; 6. Malignant pleural effusion is accompanied by clinical symptoms, such as dyspnea, chest tightness and chest pain. 7. If one of the following conditions is met: (1) They have not previously received chemotherapy, EGFR-TKI drugs, biological or immunotherapy, or other experimental treatment as the first-line treatment for advanced NSCLC (there is no restriction on EGFR T790M mutation status in newly diagnosed patients); (2) After previous first-line treatment with EGFR TKIs (e.g., gefitinib, erlotinib, etc.), the imaging findings confirmed that the disease had progressed. The tissues or peripheral blood after the last EGFR TKIs treatment were obtained, and the patients with positive EGFR T790M mutation were detected; 8. According to RECIST 1.1 criteria, there was at least one measurable lesion that did not receive radiotherapy during the screening period of imaging diagnosis; 9. ECOG score 0-2; 10. The expected survival time is not less than 12 weeks; 11. Women and men of childbearing age should agree to take medically acceptable contraceptive measures at the time of study treatment and within 3 months after the end of treatment. All women of childbearing age must have a negative pregnancy test.
Exclusion criteria
Exclusion criteria: 1. Combined with other malignant tumors (except for clinically cured cervical carcinoma in situ, basal cell or squamous cell skin cancer and papillary thyroid carcinoma); 2. The third generation of EGFR-TKI has been used; 3.Chemotherapy or immunotherapy was performed within 4 weeks before the first administration, and radiotherapy was performed within 2 weeks before the first administration; 4. Patients who had undergone surgery within 4 weeks before the first administration, except for minor operations (such as tooth extraction, etc.) that did not affect the participation in the trial as judged by the researchers; or patients who planned major surgery during the study period; 5. The symptoms or signs deteriorated obviously within 2 weeks before screening, and the researcher judged that it was not suitable to participate in the test; 6. The toxic reaction after previous treatment did not recover, and the test drug was judged as grade 2 or above according to CTCAE before administration, except for alopecia; 7. Unstable brain metastases with spinal cord compression or symptoms or requiring steroid therapy 4 weeks before enrollment. Patients with asymptomatic brain metastases or stable after treatment for more than 4 weeks and without steroid treatment can be enrolled. Patients with meningeal metastases were not included; 8. Any clinical evidence of severe or uncontrolled disease, which the researcher considers unsuitable for the clinical trial or may affect the patient's compliance with the study protocol, such as patients with hypertension who cannot be controlled after drug treatment (SBP > 160mmhg or DBP > 100mmhg), patients with active bleeding constitution, patients with active infection (such as hepatitis B, hepatitis C, HIV antibody positive, Treponema pallidum antibody positive (except those whose titer test results are negative). Active hepatitis B is defined as hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) positive, and HBV DNA >=2000 IU / ml. Active hepatitis C is defined as HCV RNA above the detection limit; 9. In the resting state, patients with abnormal results of ECG corrected QT interval (QTCF) during screening period were retested twice every time at least 4 hours. The average QTCF of three ECG examinations >=450 msec for men and >= 470 msec for women; 10. All kinds of clinically significant abnormal ECG patterns, such as complete left bundle branch block, III degree block, II degree block, PR interval > 250 msec.; 11. There are various factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome Long QT syndrome or unexplained sudden death in first-degree relatives with family history; drugs known or likely to induce QT interval prolongation and / or torsade de pointes ventricular tachycardia should be used in combination with drugs known or likely to induce QT interval prolongation and / or torsade de pointes ventricular tachycardia in the study period before the first administration of the trial drug; echocardiography: left ventricular ejection fraction (LVEF) = 50% or other investigators' judgment has clinical significance Is abnormal; 12. Severe respiratory diseases, such as interstitial lung disease, severe asthma, pulmonary embolism, etc.; 13. Any condition that affects the patient's swallowing of drugs or oral absorption disorders, such as severe chronic gastrointestinal diseases, gastrointestinal sur
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| intrapleural ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| safety;intrapleural DCR;ORR;DCR;PFS;intrapleural progression-free survival; | — |
Countries
China
Contacts
Public ContactYunhua Xu
Shanghai Chest hospital
Outcome results
None listed