bevacizumab in the treatment of malignant pleural effusions of non-squamous non-small cell lung cancer

Conditions: Malignant Pleural Effusion

Summary: the purpose of this study is to explore the efficacy and safety of different doses of bevacizumab injection in the treatment of malignant pleural effusion in patients with advanced non-squamous non-small cell lung cancer.

this study is a prospective, multicenter, randomized, phase ii clinical study. 87 patients will be recruited. group a (low dose group) intrapleural injection of bevacizumab 2.5mg/kg/times, d1, d8; 21 days for a course of treatment. subjects will received two courses of treatment if there is no termination of treatment listed in the standard. group b (medium dose group) intrapleural injection of bevacizumab 5mg/kg/times, d1, d8; 21 days for a course of treatment. subjects will received two courses of treatment if there is no termination of treatment listed in the standard. group c (high dose group) intrapleural injection of bevacizumab 7.5mg/kg/times, d1, d8; 21 days for a course of treatment. subjects will received two courses of treatment if there is no termination of treatment listed in the standard. main evaluation criteria: pleural effusion objective response rate(orr) (who standard) secondary evaluation criteria: pleural fluid time to progression (ttp), overall survival (os), orr, qol scores (quality of life questionnaire-lung cancer) and kps, and safety (nci ctcae v4.03)

Eligibility criteria:
inclusion criteria: 1. voluntarily sign informed consent; 2. non-squamous non-small cell lung cancer, newly diagnosed or previously treated with systemic chemotherapy and / or epidermal growth factor receptor (egfr) tyrosine kinase inhibitors treatment; 3. b ultrasound, chest x-ray or ct examination to a large number of pleural effusion, with a cytology confirm of malignant pleural effusion; 4. aged 18-75 years; 5. eastern cooperative oncology group (ecog) score ≤ 2; 6. survival is expected to exceed 8 weeks exclusion criteria: if any of the following criteria is met, the subject shall be excluded: 1. squamous cell carcinoma (including adenosquamous carcinoma) and small cell lung cancer (including small cell carcinoma and non-small cell mixed lung cancer); 2. in the past 2 weeks, there have been systematic anti-tumor treatment including chemotherapy (including thoracic chemotherapy), radiotherapy (excluding radiotherapy of metastatic lesions outside the thoracic radiation field), targeted therapy, immunotherapy and biotherapy; 3. the subject had received anti-vascular endothelial growth factor (vegf) small molecule tyrosine kinase inhibitors or monoclonal antibodies in the past 4 weeks; 4. the subject had participated any clinical trials in the past 4 weeks; 5. the subject had previously received bevacizumab of pleural perfusion therapy; 6. laboratory results: * white blood cell count \<3 × 109 / l, neutrophil count \<1.5 × 109 / l, platelet \<75 × 109 / l, or hemoglobin \<8g / dl; * coagulation abnormalities (inr \> 1.5 or prothrombin time (pt) \> uln + 4 seconds or activated partial thromboplastin time (aptt) \> 1.5 uln), with bleeding tendency or being treated with thrombolysis or anticoagulation; * serum total bilirubin ≥1.5 uln; alanine aminotransferase (alt) or aspartate aminotransferase (ast) ≥ 2.5 uln in the absence of liver metastases; alt or ast ≥5 uln in liver metastases; * serum albumin \<30g / l; * serum creatinine ≥ 1.5 uln or creatinine clearance \<40ml / min; * urine routine urinary protein ≥ ++, or 24 hours urine protein ≥ 1.0 g; 7. hypertension cannot be controlled by drugs; 8. heart disease with significant clinical symptoms, such as: congestive heart failure, coronary heart disease with symptom, arrhythmia hardly be controlled by drugs, myocardial infarction in 6 months, or heart failure; 9. imaging (ct or mri) showed a tumor lesion 5 mm away from the large vessels, or the presence of invasive central vasculature of the central tumor; imaging (ct or mri) showed significant cavitation or necrosis of the lung tumor; other diseases that may cause haemoptysis; 10. imaging (ct or chest radiograph) showed significant pneumothorax, fluid pneumothorax; 11. bilateral pleural cavity to a large number of effusion or encapsulated pleural effusion; 12. obvious cough blood in 6 months, or daily hemoptysis amounted to half a teaspoon (2.5ml) or more; 13. significant bleeding symptoms or with definite bleeding tendency within 12 months before randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, occult blood ++ and above, intracerebral hemorrhage, vasculitis, or with congenital or acquired coagulopathy disorders; 14. thrombosis, cancer thrombosis (including arteriovenous thrombosis, tumor thrombus, pulmonary embolism, transient ischemic attack, etc.) occurred within 12 months; 15. there are gastrointestinal obstruction, peptic ulcer, crohn's disease, ulcerative colitis and other gastrointestinal diseases or other diseases may cause gastrointestinal bleeding or perforation; 16. severe respiratory diseases, or need long-term oxygen, corticosteroid treatment of diseases such as chronic obstructive pulmonary disease, interstitial lung disease and respiratory failure; 17. the toxicity of previous antineoplastic therapies has not yet recovered to below grade 2 or has not fully recovered; 18. patients with uncontrolled central nervous system metastasis; 19. there are serious uncontrolled systemic diseases, such as nephrotic syndrome, infection, poorly controlled diabetes; 20. patients with active hiv（human immunodeficiency virus）, hbv（hepatitis b virus）, or hcv（hepatitis c virus） infection; 21. patients had undergone surgery (\<28 days) or did not heal completely, or had other unhealed wounds before the study; 22. patients known to be allergic to bevacizumab or any of the components of the drug; 23. pregnant or lactating female patients, or unwilling to take contraceptive measures of reproductive age patients (including men); 24. there is a serious psychological or mental abnormality, or lack of compliance; 25. the investigator determines other circumstances that may affect the conduct of clinical studies and the determination of findings.

Keywords: malignant pleural effusion bevacizumab