Bevacizumab in the Treatment of Malignant Pleural Effusions of Non-squamous Non-small Cell Lung Cancer

Phase 2

• Conditions: Malignant Pleural Effusion
• Interventions: Drug: Bevacizumab

• Registration Number: NCT02942043
• Lead Sponsor: Peking University Cancer Hospital & Institute

Brief 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.

Detailed Description

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)

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-10-18
• Study First Submitted QC: 2016-10-20
• Study First Posted: 2016-10-21
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-05
• Last Update Posted: 2018-11-07
• Primary Completion: 2019-05
• Study Completion: 2019-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 87

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B (medium dose group)	Bevacizumab	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 A (low dose group)	Bevacizumab	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 C (high dose group)	Bevacizumab	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.

Primary Outcome Measures

Name	Time	Method
Pleural effusion ORR	1 year

Secondary Outcome Measures

Name	Time	Method
ORR	1 year
Pleural fluid TTP	1 year
OS	1 year
QOL scores	2 month
Safety (NCI CTCAE V4.03)	2 month

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China