Determining the feasibility and diagnostic accuracy in terms of sensitivity and specificity of intraoperative detection of peritoneal carcinomatosis of colorectal origin by intraoperative fluorescence imaging using the VEGF-targeting optical imaging…
ID
Source
Brief title
Condition
- Peritoneal and retroperitoneal conditions
- Miscellaneous and site unspecified neoplasms benign
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Determination of sensitivity ands specificity data of the sampled (non-)
fluorescent tissue acquired intraoperatively compared to standard
histopathological examination for the presence of tumor tissue. (10 samples per
patient).
- Localization and (semi) quantification of a fluorescent signal of tumor
tissue and surrounding tissue after post-processing of the in vivo required
data.
- In vivo NIR fluorescence quantification vs. ex vivo VEGF levels in biopsies
and additional ex vivo analyses (using immunohistochemistry (IHC).
Secondary outcome
Improving the detection rate of peritoneal carcinomatosa using MFR imaging, for
purposes of better staging by calculating the peritoneal carcinomatosis index
(PCI) based on fluorescence detection
Background summary
This project consists of the realization and clinical validation of
intraoperative imaging of tumor tissue in the case of peritoneal carcinomatosis
(PC) of colorectal origin. Currently, it is not possible to determine the
microscopic extent of peritoneal dissemination of cancer during surgery. The
decision whether or not a patient could benefit from surgery or whether the
disease can be deemed as resectable or not, is based on the impression of the
visual inspection of the surgeon. It seems reasonable that by resecting
microscopic in addition to macroscopic disease, the number of R0 resections
will increase and outcome will improve. By applying a method to assess the
extent of peritoneal dissemination of cancer through a novel targeted optical
fluorescent imaging methodology, both the staging and the resection will be
more optimal.
VEGF-A (Vascular Endothelial Growth Factor - A) is highly upregulated in tumor
tissue of patients with PC of colorectal origin (own UMCG data set: (n=35),
100%) and can be targeted by using the VEGF antibody Bevacizumab (Avastin).
The objective of the proposed study is the intraoperative detection of tumor
tissue of peritoneal carcinomatosis of colorectal origin by using a
near-infrared fluorophore, 800CW, conjugated to bevacizumab resulting in a
bevacizumab-IRDye800CW imaging compound, administered at micro dose levels
(i.e. 30 nmol, or 4,5 mg). The compound has been shown to be safe at a
microdosing regimen in an earlier phase I clinical study in patients with
breast cancer executed at the UMCG.
Medical and surgical oncologists, pharmacists, chemists, and molecular
biologists experienced in carrying out clinical translational studies using
bevacizumab-IRDye800CW are involved in this project.
Study objective
Determining the feasibility and diagnostic accuracy in terms of sensitivity and
specificity of intraoperative detection of peritoneal carcinomatosis of
colorectal origin by intraoperative fluorescence imaging using the
VEGF-targeting optical imaging agent bevacizumab-IRDye800CW in a pilot study
design . Ex vivo immunohistochemical analyses and fluorescence microscopy will
be used to confirm the presence of VEGF-A and bevacizumab-IRDye800CW in
excised tumor tissue.
Study design
Interventional pilot study: non-randomized, open label, uncontrolled with
single group assignment.
The new VEGF-targeting fluorescent tracer (bevacizumab-IRDye800CW) will be
administered intravenously two days before the surgical procedure is scheduled
(procedure at day 3). During the imaging procedure we will compare the tumour
spots that were identified using bevacizumab-IRDye800CW with the results of the
visual inspection by the surgeon. Subsequently, the NIR fluorescent signal of
different lesions will be quantified. Tumour spots will be imaged using
different angles to get optimal excitation of the tissue.
Biopsies will be taken separately from areas with fluorescent and
no-fluorescent spots during epi-illumination for ex vivo analyses (totalling 5
fluorescent vs 5 non-fluorescent). In addition, video registration will be
performed of parts of the imaging procedure.
Intervention
Patients scheduled for a HIPEC procedure for peritoneal carcinomatosis of
colorectal origin will be consented for this study. There will be three study
related visits. During a screening visit (visit 1), eligibility will be
evaluated and patient characteristics will be collected. During the second
visit 4.5 mg of bevacizumab-IRDye800CW will be administered intravenously. The
patient will then be observed for 1 hour post administration. One day after
administration of the tracer (visit 3 one day before surgery) the patient is
administered to the hospital as in the standard procedure. During the HIPEC
procedure the fluorescent imaging will be performed and data acquired.
Study burden and risks
In this study, safety data related to (the administration of) the tracer will
be collected and evaluated. Based on clinical experience in the first thirteen
breast cancer patients (NL37479.042.11), animal toxicity studies and the fact
that we will administrate a low, non-therapeutic (single dose 4.5 mg
bevacizumab-IRDye800CW vs 5 mg/kg bevacizumab in therapeutics), no adverse
events are expected following administration of bevacizumab-IRDye800CW. In the
first thirteen breast cancer patients, included in NL37479.042.11, no toxicity
and adverse reaction were observed. To assess more information regarding the
safety of bevacizumab-IRDye800CW in the current study, safety data will be
collected comparable as done in NL37479.042.11. The investigators will have
close contact with the (same) investigators of NL37479.042.11 regarding safety
data related to bevacizumab-IRDye800CW, collected in both studies.
In the current protocol, patients will undergo the HIPEC procedure with
additional fluorescence imaging of the tumour spots found during the debulking
procedure. The imaging procedure will add a maximum of 45 minutes of operation
time.
The time investment of the subjects is considered reasonable. The procedures
at the screening visit and the tracer administration visit will take around 4
hours total.
Hanzeplein 1
Groningen 9713 EZ
NL
Hanzeplein 1
Groningen 9713 EZ
NL
Listed location countries
Age
Inclusion criteria
• Age >= 18 years.
• Patients with histopathological proven peritoneal carcinomatosis from colorectal origin who are scheduled to the HIPEC procedure
• Patient is considered to be mentally and physically fit for the HIPEC procedure as judged by the responsible physician
• WHO performance score 0-2
• Signed written informed consent.
Exclusion criteria
• Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.
• Distance metastasis (liver / lungs)
• Medical or psychiatric conditions that compromise the patient*s ability to give informed consent.
• Concurrent uncontrolled medical conditions.
• Pregnancy or breast feeding.
• Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 12 months.
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003066-14-NL |
| CCMO | NL45588.042.13 |
| OMON | NL-OMON27201 |