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

Primary Purpose

Malignant Pleural Effusion

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Bevacizumab
Sponsored by
Peking University Cancer Hospital & Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Effusion focused on measuring Malignant pleural effusion, Bevacizumab

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group A (low dose group)

Group B (medium dose group)

Group C (high dose group)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Pleural effusion ORR

Secondary Outcome Measures

Pleural fluid TTP
OS
ORR
QOL scores
Safety (NCI CTCAE V4.03)

Full Information

First Posted
October 18, 2016
Last Updated
November 5, 2018
Sponsor
Peking University Cancer Hospital & Institute
Collaborators
Peking University First Hospital, Peking University Third Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02942043
Brief Title
Bevacizumab in the Treatment of Malignant Pleural Effusions of Non-squamous Non-small Cell Lung Cancer
Official Title
A Prospective, Multicenter, Randomized Controlled Clinical Trial of Bevacizumab in the Treatment of Malignant Pleural Effusions of Non-squamous Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 2016 (undefined)
Primary Completion Date
May 2019 (Anticipated)
Study Completion Date
October 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University Cancer Hospital & Institute
Collaborators
Peking University First Hospital, Peking University Third Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Effusion
Keywords
Malignant pleural effusion, Bevacizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
87 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A (low dose group)
Arm Type
Experimental
Arm Description
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.
Arm Title
Group B (medium dose group)
Arm Type
Experimental
Arm Description
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.
Arm Title
Group C (high dose group)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pleural effusion ORR
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Pleural fluid TTP
Time Frame
1 year
Title
OS
Time Frame
1 year
Title
ORR
Time Frame
1 year
Title
QOL scores
Time Frame
2 month
Title
Safety (NCI CTCAE V4.03)
Time Frame
2 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntarily sign informed consent; 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; B ultrasound, chest X-ray or CT examination to a large number of pleural effusion, with a cytology confirm of malignant pleural effusion; Aged 18-75 years; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; Survival is expected to exceed 8 weeks Exclusion Criteria: If any of the following criteria is met, the subject shall be excluded: Squamous cell carcinoma (including adenosquamous carcinoma) and small cell lung cancer (including small cell carcinoma and non-small cell mixed lung cancer); 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; The subject had received anti-vascular endothelial growth factor (VEGF) small molecule tyrosine kinase inhibitors or monoclonal antibodies in the past 4 weeks; The subject had participated any clinical trials in the past 4 weeks; The subject had previously received bevacizumab of pleural perfusion therapy; 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; Hypertension cannot be controlled by drugs; 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; 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; Imaging (CT or chest radiograph) showed significant pneumothorax, fluid pneumothorax; Bilateral pleural cavity to a large number of effusion or encapsulated pleural effusion; Obvious cough blood in 6 months, or daily hemoptysis amounted to half a teaspoon (2.5ml) or more; 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; Thrombosis, cancer thrombosis (including arteriovenous thrombosis, tumor thrombus, pulmonary embolism, transient ischemic attack, etc.) occurred within 12 months; There are gastrointestinal obstruction, peptic ulcer, Crohn's disease, ulcerative colitis and other gastrointestinal diseases or other diseases may cause gastrointestinal bleeding or perforation; Severe respiratory diseases, or need long-term oxygen, corticosteroid treatment of diseases such as chronic obstructive pulmonary disease, interstitial lung disease and respiratory failure; The toxicity of previous antineoplastic therapies has not yet recovered to below grade 2 or has not fully recovered; Patients with uncontrolled central nervous system metastasis; There are serious uncontrolled systemic diseases, such as nephrotic syndrome, infection, poorly controlled diabetes; Patients with active HIV(human immunodeficiency virus), HBV(hepatitis B virus), or HCV(hepatitis C virus) infection; Patients had undergone surgery (<28 days) or did not heal completely, or had other unhealed wounds before the study; Patients known to be allergic to bevacizumab or any of the components of the drug; Pregnant or lactating female patients, or unwilling to take contraceptive measures of reproductive age patients (including men); There is a serious psychological or mental abnormality, or lack of compliance; The investigator determines other circumstances that may affect the conduct of clinical studies and the determination of findings.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Fang
Phone
+86-010-88196459
Email
bcht2_mj@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Di Wu
Phone
+86-010-88196459
Email
lucia8810@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jian Fang
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Fang
Phone
+86-010-88196459
Email
bcht2_mj@163.com
First Name & Middle Initial & Last Name & Degree
Di Wu
Phone
+86-010-88196459
Email
lucia8810@sina.com
First Name & Middle Initial & Last Name & Degree
Jian Fang

12. IPD Sharing Statement

Plan to Share IPD
Undecided
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Citation
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Bevacizumab in the Treatment of Malignant Pleural Effusions of Non-squamous Non-small Cell Lung Cancer

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