The main objective of this pilot study is to investigate the feasibility of fluorescence imaging with the fluorescence agent bevacizumab-800CW to detect endometriosis tissue.
ID
Source
Brief title
Condition
- Reproductive neoplasms female benign
- Obstetric and gynaecological therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The aim of this feasibility study is to investigate whether the fluorescent
agent bevacizumab-800CW can specifically target endometriosis lesions as
determined by ex vivo fluorescence imaging techniques. This will be confirmed
by standard H/E staining, VEGF immunohistochemistry, confocal laser
endomicroscopy (CLE), spectroscopy and histopathological fluorescence
microscopy. In this way, future intra-operative quantification and
visualisation of endometriosis can be evaluated.
Secondary outcome
The secondary objective of this study is to investigate whether the Olympus
NIRlaparoscope is able to detect endometriosis lesions intraoperatively by
fluorescence imaging after micro dosing injection of 4,5 mg bevacizumab-800CW.
Background summary
The aim of this pilot project is to determine the feasibility of fluorescence
imaging to improve the treatment of endometriosis in the future. Incomplete
resection of endometriosis lesions often results in recurrence of symptoms and
the need for repeated surgery, with considerable associated morbidity. The
value of the fluorescence imaging with the near infrared (NIR) fluorescent
agent bevacizumab-800CW will be evaluated in vivo and ex vivo to determine the
feasibility in specific detection of endometriosis lesions in patients that are
undergoing surgery for endometriosis. Secondly, there will be a clinical
validation of intra-operative fluorescence imaging in the laparoscopic
treatment of endometriosis using a CE-certified Olympus NIR laparoscope. This
intra-operative imaging technique can be used as a tool to detect more lesions,
resulting in a more radical resection and lower risk of recurrence of symptoms
compared to current standard laparoscopy. In a previous
immunohistochemicaltissue study, VEGF-A was shown to be significantly
over-expressed inendometriosis tissue compared to surrounding normal healthy
tissue, justifying the use of the VEGF-A-targeted bevacizumab-800CW.In a recent
clinical trial in patient with breast cancer, colorectal cancer, and
oesophageal cancerbevacizumab-800CW appeared to be safe and specific for
VEGF-A(NCT01508572,NCT01972373, NCT02129933, NCT02113202 at
www.clinicaltrials.gov).
Study objective
The main objective of this pilot study is to investigate the feasibility of
fluorescence imaging with the fluorescence agent bevacizumab-800CW to detect
endometriosis tissue.
Study design
Interventional feasibility study: non-randomized, open label, uncontrolled with
single group assignment. Patients planned to undergo laparoscopic surgery for
endometriosis will be consented for this study. Three days before surgery,
patients receive an intravenous injection of 4,5 mg bevacizumab-800CW. During
surgery, white light and fluorescence images will be taken. All clinical
suspected endometriosis lesions are removed by gold standard white light
imaging. To be able to correlate the absence or presence of fluorescent signals
with endometriosis, surgeons will biopsy non-suspicous lesions when fluorescent
(up to 5) and when non-fluorescent (up to 5). Directly after surgery the
surgeon indicates the suspicious and unsuspected lesions at the surgical
specimen. The surgical specimen will be scanned in the BlackBox fluorescence
imaging system to evaluate presence of fluorescence in these lesions. Ex vivo
correlation between fluorescent signals in endometriosis specimen by
fluorescence flatbed scanning haematoxylin/eosin and VEGF immunohistochemistry
will performed using ex vivo imaging techniques. These procedures are all
carried out at the University Medical Centre Groningen, in a collaboration
between the Department of Surgery, Nuclear Medicine and Molecular Imaging and
Intensive Care, the Department of Gynaecology and the Department of Pathology.
Intervention
Three days before surgery, the patient receives an intravenous injection of 4,5
mg bevacizumab-800CW. During laparoscopy, white light and fluorescence images
are taken with the Olympus NIR camera system and all endometriosis tissue is
taken out by gold standard white light imaging. Up to 5 fluorescent and up to 5
non-fluorescent biopsies are taken of non-suspicious lesions. White light
fluorescence images are taken ex vivo of the surgical specimen, to confirm if
the tracer accumulates specifically in endometriosis tissue. Biopsies of
fluorescent and non-fluorescent peritoneal surface tissue will be taken only if
technical feasible and safe for reasons of comparison.
Study burden and risks
The burden associated with participation consists of an intravenous injection
of 4,5 mg bevacizumab-800CW threedays before the surgical procedure, requiring
admission to the hospital for one to one and a half hour. Additionally, the
surgical procedure will be slightly
longer, due to the use of the intraoperative fluorescence imaging (no more than
30 minutes).
1. The possible serious adverse event for injection of bevacizumab-800CW is an
allergic and anaphylactic reaction, as described in the IMPD of METc
application 2011/196, but has not been observed in more than 100 patients
currently injected with the tracer. Potential other adverse events are
transient and mild (nausea, vomiting, flushing, chest discomfort), but have not
been observed in now more than 100 patients injected with the tracer.
2. The possible effect of prolonged anaesthesia because of testing the camera
system and detection of residual disease is limited in itself because of a
total extra surgery time of no longer than 30 minutes.
3. There is no risk or burden of using the intraoperative imaging device; all
mandatory tests have been executed and tested to be safe for use in patients
and the camera system is confirmed with a CE marking.
4. There is no risk of infection; the imaging device is sterilized according to
standard procedures at the Central Sterilisation Unit at the UMCG to prevent
infection during surgery.
5. If the surgeon considers it safe, biopsies are taken from clinical
non-suspicious lesions when fluorescent (up to 5) and non-fluorescent
surrounding tissue (also up to 5). The risk of complications due to these
biopsies is considered as low.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
1. Females aged * 18 years
2. Scheduled for surgery for the treatment of endometriosis
3. WHO performance score of 0-2
4. Written informed consent
For female subjects who are of childbearing potential, are premenopausal with intact reproductive organs or are less than 2 years post-menopausal:
4. A negative serum pregnancy test prior to receiving the second generation tracer
5. Willing to ensure that she or her partner uses effective contraception during the trial and for 6 months thereafter.
Exclusion criteria
1. Medical or psychiatric conditions that compromise the patient*s ability to give informed consent ;2. Pregnancy
3. History of infusion reactions to Bevacizumab or other monoclonal antibody therapies
4. Significant renal, cardiac, or pulmonary disease (ASA III-IV)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-001362-28-NL |
| ClinicalTrials.gov | NCT02975219 |
| CCMO | NL57269.042.16 |