Pleural Effusion, MalignantPhase 1BEVAPNCT02250118
Intrapleural Bevacizumab After Pleural Drainage in the Context of Breast Cancer
A Phase 1 study testing Bevacizumab in people with Pleural Effusion, Malignant and Breast Cancer, run by Institut Curie at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Effusion, Malignant, Breast Cancer
- What is being tested?
- Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteFrance
- Study dates
- 9 Dec 2014to 17 Oct 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Expected life span > 2 months
- Corticosteroids authorized if started less than 15 days before enrollment and no dose modification will be allowed during treatment
- 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
- Cardiac Function satisfactory: Left Ventricular Ejection Fraction (LVEF) determined by myocardial scintigraphy or echocardiography
- 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
- Patient receiving a social security system
- Signed inform consent
Who cannot join
- 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.
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- 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
- 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.
- 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.
- 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.
- Impossibility to follow the calendar of exams because of geographic, social or psychological reasons.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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
- Being tested
- Bevacizumab
- Keywords
- pleural, effusion, breast, cancer
- Medical subject headings
- Pleural Effusion, Malignant, Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Intrapleural Bevacizumab
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab | Experimental | Intrapleural use: range 0.5 - 5 mg/kg Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days after intrapleural injection
Secondary outcomes (7)
Study of the pleural and serum pharmacokinetics
Pharmacokinetics of bevacizumab just before administration and 1 hour after treatment on Day 1, and at D15, D30, D60 and D90.
Measured: 90 days
Study of pleural and serum Vascular Endothelial Growth Factor (VEGF) levels
Pleural and serum VEGF levels just before administration and 1 hour after treatment on Day 1, and at D15, D30, D60 and D90.
Measured: 90 days
Determination of time until new punction or death
Response to treatment assessed by the time to new puncture
Measured: 2 years
Total number of pleural drainage procedures
Measure of the total number of pleural drainage procedures at D15, D30, D60 and D90.
Measured: 90 days
Drainage-free survival and overall survival
Drainage-free survival and overall survival Evaluation of survival without punction and overall survival
Measured: 2 years
Evaluation of dyspnoea
Measure by dyspnoea scale and peak flow at D15, D30, D60 and D90
Measured: 90 days
Evaluation of quality of life
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2014 (estimated)
- Study start9 Dec 2014
- Primary completion12 Apr 2017
- Study completion17 Oct 2017
Why it stopped: Insufficient Recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pleural Effusion, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Curie
- Sponsor type
- University, hospital or other
- Collaborators
- Henri Mondor University Hospital
- Responsible party
- Sponsor
- Investigators
- Maya Gutierrez, MD, Principal investigator, Institut Curie - Hôpital René Huguenin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02250118
- Sponsor's protocol ID
- IC 2014-02
- Other IDs
- 2014-000654-11, 2014
- Acronym
- BEVAP
- Status last verified
- May 2017
- First submitted
- 8 Sep 2014
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02250118
- Acronym / sponsor ID
- BEVAP / IC 2014-02
- Conditions
- Pleural Effusion, Malignant, Breast Cancer
- Keywords
- pleural, effusion, breast, cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient Recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Institut CurieUniversity, hospital or other
- Collaborators
- Henri Mondor University Hospital
- Study start
- 9 Dec 2014 (actual)
- Primary completion
- 12 Apr 2017 (actual)
- Study completion
- 17 Oct 2017 (actual)
- First posted
- 26 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab | Experimental | Drug: BevacizumabIntrapleural use: range 0.5 - 5 mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (20 listed)
- 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):
- Purulent pleural effusion.
- Macroscopically haemorrhagic pleural effusion.
- Bilateral metastasis pleurisy requiring punctures on both sides.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinIntrapleural Bevacizumab | Drug | Bevacizumab |
Primary outcome
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.
7 secondary outcomes
Study of the pleural and serum pharmacokinetics
Time frame: 90 days
Study of pleural and serum Vascular Endothelial Growth Factor (VEGF) levels
Time frame: 90 days
Determination of time until new punction or death
Time frame: 2 years
Total number of pleural drainage procedures
Time frame: 90 days
Drainage-free survival and overall survival
Time frame: 2 years
Evaluation of dyspnoea
Time frame: 90 days
Evaluation of quality of life
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Insufficient Recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maya Gutierrez, MD principal investigator
Institut Curie - Hôpital René Huguenin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab in people with Pleural Effusion, Malignant and Breast Cancer, run by Institut Curie at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Insufficient Recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose (MTD) (time frame: 90 days after intrapleural injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.