Intrapleural Bevacizumab After Pleural Drainage in the Context of Breast Cancer

NCT02250118 | Terminated Phase 1 DMC

• 2 other identifiers: IC 2014-022014-000654-11
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Metastatic pleural effusion is a common complication of late-stage cancer and reduces the quality of life and survival of patients. The survival of patients with recurrent pleurisy by uncontrolled local or systemic treatment is less than 6 months. It is important to develop specific therapies to improve the quality of life and survival of patients with metastatic pleurisy. Bevacizumab is a monoclonal anti vascular endothelial growth factor (VEGF) which has proven effective in many indications in oncology. Vascular endothelial growth factor (VEGF) is an angiogenic factor which increases endothelial permeability. It plays a central role in many tumors of epithelial origin. In this context, it is legitimate to ask whether an antiangiogenic targeting VEGF may be effective in patients with metastatic pleurisy by decreasing local blood supply and over-permeability. No study has been interested in the intra-pleural pharmacokinetics of monoclonal antibodies and there are no predictive or prognostic biomarkers for metastatic pleural effusions. The investigators believe that intrapleural administration of bevacizumab will reduce the pleural vasculature permeability. It will neutralize VEGF present in pleural fluid and reduce the replenishment of effusion due to its prolonged half-life of 21 days. The investigators therefore propose a phase I study to determine the maximum tolerated dose and the recommended dose for phases II, studying the pharmacokinetics of intrapleural bevacizumab administered by an implantable device after evacuating a symptomatic metastatic pleurisy as part of a mammary carcinoma. The VEGF intrapleural levels and serum will be study and the time until a new puncture. Dyspnea will be evaluated as well as its impact on quality of life.

Conditions

Pleural Effusion, Malignant; Breast Cancer

Keywords

pleural; effusion; breast; cancer

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD) according to safety of intrapleural bevacizumab at dose levels of 1 mg/kg, 3 mg/kg and 5 mg/kg administered by pleural catheter after drainage of symptomatic malignant pleural effusion in a context of breast cancer.

  90 days after intrapleural injection

Secondary Outcomes (7)

• Study of the pleural and serum pharmacokinetics

  90 days

• Study of pleural and serum Vascular Endothelial Growth Factor (VEGF) levels

  90 days

• Determination of time until new punction or death

  2 years

• Total number of pleural drainage procedures

  90 days

• Drainage-free survival and overall survival

  2 years

Study Arms (1)

Bevacizumab

EXPERIMENTAL

Intrapleural use: range 0.5 - 5 mg/kg

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Intrapleural Bevacizumab

Also known as: Avastin

Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Patient with histologically documented pleural effusion in a type of breast carcinoma in exudate or with no other identified cause. In the absence of positive cytology, will ensure that there is no other cause of the patient's history may explain the effusion.
• Unilateral or bilateral malignant pleural effusion but requiring drainage on only one side.
• Patient presenting an indication for pleural implantable device, means that requiring at least one pleural drainage.
• Patient aged 18 years old or more and without measure of legal protection
• Subject female or male
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
• Expected life span \> 2 months
• Corticosteroids authorized if started less than 15 days before enrollment and no dose modification will be allowed during treatment
• Haemoglobin ≥ 8 g/dl (transfusion authorized)
• Neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 100 000/mm3
• International Normalized Ratio (INR) ≤ 1.5 and/or Prothrombin Ratio (TR) ≥ 70 % and Partial Thromboplastin Time (PTT) ≤ 1.5
• Aspartate Aminotransferase Test (AST), Alanine Aminotransferase Test (ALT), Gamma-Glutamyl Transpeptidase (GGT), Alk Phos ≤ 3 times Unit Line Number (ULN), bilirubin ≤ 40 μmol/L
• Lactate Dehydrogenase (LDH) ≤ 1,5 times ULN
• Albumin ≥ 28 g/dL

You may not qualify if:

• Pregnant or lactating women or childbearing potential refusing methods of birth control
• Transudative pleural effusion: pleural protein \< 30 g/L and/or Light's criteria when pleural protein is not indicative. Light's criteria are as follows (for diagnosis of transudative):
• Pleural protein/serum protein ratio \< 0.5
• Pleural LDH/serum LDH ratio \< 0.6
• Pleural LDH \< two-thirds the upper limit of normal of serum LDH
• Purulent pleural effusion.
• Macroscopically haemorrhagic pleural effusion.
• Bilateral metastasis pleurisy requiring punctures on both sides.
• Any co morbidity considered to be incompatible with participation in the study, according to the investigator, particularly: untreated infectious disease, chronic respiratory insufficiency, chronic renal insufficiency, Child Pugh B or C, hepatocellular insufficiency; chronic heart failure not controlled by appropriate medical treatment.
• Contraindications to intrapleural administration of bevacizumab:
• Non-controlled arterial or venous thromboembolism
• Major surgery during the previous month or planned after study
• Known, non treated brain metastases
• Known hypersensitivity to bevacizumab or one of its excipients
• Hypersensitivity to Chinese hamster ovary cell (CHO) products or other human recombinant or humanized antibodies

Sponsors & Collaborators

• Institut Curie: lead
• Henri Mondor University Hospital: collaborator

Study Sites (1)

Institut Curie - Hôpital René Huguenin

Saint-Cloud, 92210, France

Location

MeSH Terms

Conditions

Pleural Effusion, Malignant; Breast Neoplasms; Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue 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

• Maya Gutierrez, MD

  Institut Curie - Hôpital René Huguenin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 26, 2014
• Study Start: December 9, 2014
• Primary Completion: April 12, 2017
• Study Completion: October 17, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-05

Locations

FR (1)