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

NCT02942043 | Unknown Phase 2

• 1 other identifier: 20160204
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Pleural Effusion

Keywords

Malignant pleural effusion; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Pleural effusion ORR

  1 year

Secondary Outcomes (5)

• Pleural fluid TTP

  1 year

• OS

  1 year

• ORR

  1 year

• QOL scores

  2 month

• Safety (NCI CTCAE V4.03)

  2 month

Study Arms (3)

Group A (low dose group)

EXPERIMENTAL

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.

Drug: Bevacizumab

Group B (medium dose group)

EXPERIMENTAL

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.

Drug: Bevacizumab

Group C (high dose group)

EXPERIMENTAL

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.

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

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.

Also known as: Avastin

Group A (low dose group); Group B (medium dose group); Group C (high dose group)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead
• Peking University First Hospital: collaborator
• Peking University Third Hospital: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Related Publications (16)

• Du N, Li X, Li F, Zhao H, Fan Z, Ma J, Fu Y, Kang H. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol Rep. 2013 Jun;29(6):2332-40. doi: 10.3892/or.2013.2349. Epub 2013 Mar 15.

  PMID: 23525453 BACKGROUND

• Medford AR, Maskell NA. A national survey of oncologist and chest physicians' attitudes towards empirical anti-oestrogen therapy, early pleurodesis and preference of sclerosing agent in malignant breast and ovarian pleural disease. Palliat Med. 2005 Jul;19(5):430-1. doi: 10.1191/0269216305pm1033xx. No abstract available.

  PMID: 16111068 RESULT

• Seto T, Ushijima S, Yamamoto H, Ito K, Araki J, Inoue Y, Semba H, Ichinose Y; Thoracic Oncology Group. Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional phase II trial. Br J Cancer. 2006 Sep 18;95(6):717-21. doi: 10.1038/sj.bjc.6603319. Epub 2006 Aug 29.

  PMID: 16940982 RESULT

• Numnum TM, Rocconi RP, Whitworth J, Barnes MN. The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol. 2006 Sep;102(3):425-8. doi: 10.1016/j.ygyno.2006.05.018. Epub 2006 Jun 23.

  PMID: 16797681 RESULT

• Pichelmayer O, Gruenberger B, Zielinski C, Raderer M. Bevacizumab is active in malignant effusion. Ann Oncol. 2006 Dec;17(12):1853. doi: 10.1093/annonc/mdl143. Epub 2006 Jun 21. No abstract available.

  PMID: 16790519 RESULT

• Kesterson JP, Mhawech-Fauceglia P, Lele S. The use of bevacizumab in refractory ovarian granulosa-cell carcinoma with symptomatic relief of ascites: a case report. Gynecol Oncol. 2008 Dec;111(3):527-9. doi: 10.1016/j.ygyno.2008.07.015. Epub 2008 Aug 16.

  PMID: 18710781 RESULT

• Pichelmayer O, Zielinski C, Raderer M. Response of a nonmalignant pleural effusion to bevacizumab. N Engl J Med. 2005 Aug 18;353(7):740-1. doi: 10.1056/NEJM200508183530722. No abstract available.

  PMID: 16107633 RESULT

• Bae SH, Hwang JY, Kim WJ, Yoon HH, Kim JM, Nam YH, Baek HG, Cho YR, Park SY, Kim JH, Kim SH, Park TH, Lee GN, Rha SH, Kim YD. A case of cardiac amyloidosis with diuretic-refractory pleural effusions treated with bevacizumab. Korean Circ J. 2010 Dec;40(12):671-6. doi: 10.4070/kcj.2010.40.12.671. Epub 2010 Dec 31.

  PMID: 21267391 RESULT

• Kitamura K, Kubota K, Ando M, Takahashi S, Nishijima N, Sugano T, Toyokawa M, Miwa K, Kosaihira S, Noro R, Minegishi Y, Seike M, Yoshimura A, Gemma A. Bevacizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer with malignant pleural effusion. Cancer Chemother Pharmacol. 2013 Feb;71(2):457-61. doi: 10.1007/s00280-012-2026-4. Epub 2012 Nov 21.

  PMID: 23178954 RESULT

• Hama M, Komatsu Y, Hachiya T. [A case of lung cancer showing marked reduction of pleural effusion by bevacizumab in combination with carboplatin and paclitaxel]. Gan To Kagaku Ryoho. 2011 Nov;38(11):1877-9. Japanese.

  PMID: 22083202 RESULT

• Mitsuhiro Fuji, Shin-Ichiro Iwakami1, Hiroaki Ihara. Efficacy and safety of chemotherapy containing bevacizumab in patients with non-small cell lung cancer with malignant pleural effusion. Respirology. 2013;18 (Suppl.4): 87

  RESULT

• Masago K, Fujimoto D, Fujita S, Hata A, Kaji R, Ohtsuka K, Okuda C, Takeshita J, Katakami N. Response to bevacizumab combination chemotherapy of malignant pleural effusions associated with non-squamous non-small-cell lung cancer. Mol Clin Oncol. 2015 Mar;3(2):415-419. doi: 10.3892/mco.2014.457. Epub 2014 Nov 19.

  PMID: 25798278 RESULT

• Tamiya M, Tamiya A, Yamadori T, Nakao K, Asami K, Yasue T, Otsuka T, Shiroyama T, Morishita N, Suzuki H, Okamoto N, Okishio K, Kawaguchi T, Atagi S, Kawase I, Hirashima T. Phase2 study of bevacizumab with carboplatin-paclitaxel for non-small cell lung cancer with malignant pleural effusion. Med Oncol. 2013;30(3):676. doi: 10.1007/s12032-013-0676-7. Epub 2013 Aug 8.

  PMID: 23925664 RESULT

• El-Shami K, Elsaid A, El-Kerm Y. Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites. J Clin Oncol.2007;25(18 suppl):9043

  RESULT

• Hamilton CA, Maxwell GL, Chernofsky MR, Bernstein SA, Farley JH, Rose GS. Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer. Gynecol Oncol. 2008 Dec;111(3):530-2. doi: 10.1016/j.ygyno.2008.04.028. Epub 2008 Jun 18.

  PMID: 18561992 RESULT

• Di W, Yue C, Ziran Z, Jie Z, Jun N, Ling D, Weiheng H, Xiaoling C, Xiangjuan M, Guangming T, Jindi H, Sen H, Yang W, Jieran L, Jian F. A phase II study of bevacizumab in non-squamous, non-small-cell lung cancer patients with malignant pleural effusion. Future Oncol. 2022 Feb;18(6):669-677. doi: 10.2217/fon-2021-1035. Epub 2022 Jan 26.

  PMID: 35080187 DERIVED

MeSH Terms

Conditions

Pleural Effusion, Malignant

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jian Fang

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Fang

CONTACT

+86-010-88196459; bcht2_mj@163.com

Di Wu

CONTACT

+86-010-88196459; lucia8810@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of thoracic oncology

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 21, 2016
• Study Start: October 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: October 1, 2019
• Last Updated: November 7, 2018

Record last verified: 2018-11

Locations

CN (1)