Intrapleural Bevacizumab After Pleural Drainage in the Context of Breast Cancer (BEVAP)

November 2, 2017 updated by: Institut Curie

Phase I Study to Determine the Maximum Tolerated Dose and Evaluate the Pharmacokinetics of Intrapleural Bevacizumab After Pleural Drainage in Patients With Symptomatic Malignant Pleural Effusion in the Context of Breast Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Saint-Cloud, France, 92210
        • Institut Curie - Hopital Rene Huguenin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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.
  2. Unilateral or bilateral malignant pleural effusion but requiring drainage on only one side.
  3. Patient presenting an indication for pleural implantable device, means that requiring at least one pleural drainage.
  4. Patient aged 18 years old or more and without measure of legal protection
  5. Subject female or male
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
  7. Expected life span > 2 months
  8. Corticosteroids authorized if started less than 15 days before enrollment and no dose modification will be allowed during treatment

  9. Adequate biological functions 14 days before inclusion:

    • 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
    • Creatinine clearance ≥ 45 mL/min according to the Modification of the Diet in Renal Disease formula (MDRD)
    • Proteinuria ≤ 1g/dL in the absence of tract infection
  10. Cardiac Function satisfactory: Left Ventricular Ejection Fraction (LVEF) determined by myocardial scintigraphy or echocardiography
  11. Females of childbearing potential must take acceptable methods of birth control during the complete duration of treatment and serum pregnancy tests must be negative at the inclusion. Men must agree to use a condom if his partner is of child bearing potential
  12. Patient receiving a social security system
  13. Signed inform consent

Exclusion Criteria:

  1. Pregnant or lactating women or childbearing potential refusing methods of birth control

  2. 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
  3. Purulent pleural effusion.
  4. Macroscopically haemorrhagic pleural effusion.
  5. Bilateral metastasis pleurisy requiring punctures on both sides.
  6. 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.

  7. 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
    • Intravenous administration of bevacizumab planned or underway in the usual cancer treatment (≥ 3 weeks wash out from the intrapleural injection)
    • Radiotherapy including lung field concerned since the administration of the product until the end of the study.
  8. Diagnosis of any second malignancy within the last 5 years, except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for > 3 years.
  9. Patients can't participate in another clinical trial with another experimental anti-cancer drug therapy simultaneously for 90 days. No exclusion period is required after the end of the trial visit.
  10. Impossibility to follow the calendar of exams because of geographic, social or psychological reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Bevacizumab
Intrapleural use: range 0.5 - 5 mg/kg
Drug: Bevacizumab
Intrapleural Bevacizumab
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To determine the maximum tolerated dose (MTD)
Time Frame: 90 days after intrapleural injection
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Study of the pleural and serum pharmacokinetics
Time Frame: 90 days
Pharmacokinetics of bevacizumab just before administration and 1 hour after treatment on Day 1, and at D15, D30, D60 and D90.
90 days
Study of pleural and serum Vascular Endothelial Growth Factor (VEGF) levels
Time Frame: 90 days
Pleural and serum VEGF levels just before administration and 1 hour after treatment on Day 1, and at D15, D30, D60 and D90.
90 days
Determination of time until new punction or death
Time Frame: 2 years
Response to treatment assessed by the time to new puncture
2 years
Total number of pleural drainage procedures
Time Frame: 90 days
Measure of the total number of pleural drainage procedures at D15, D30, D60 and D90.
90 days
Drainage-free survival and overall survival
Time Frame: 2 years
Drainage-free survival and overall survival Evaluation of survival without punction and overall survival
2 years
Evaluation of dyspnoea
Time Frame: 90 days
Measure by dyspnoea scale and peak flow at D15, D30, D60 and D90
90 days
Evaluation of quality of life
Time Frame: 2 years
Quality of life (QLQ-C30) questionnaire according to European Organisation for Research and Treatment of Cancer (EORTC) and FACIT questionnaire Dyspnoea 10 Short Form at D15, D30, D60 and D90 and every 6 month during 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut Curie

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Henri Mondor University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Maya Gutierrez, MD, Institut Curie - Hopital Rene Huguenin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 9, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 12, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 17, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IC 2014-02
  • 2014-000654-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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