The main objective is to study if the conjugate bevacizumab-IRDye800CW accumulates more in sinonasal inverted papilloma than in normal sinonasal mucosa, with a TBR of *2 as cutoff value.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Macroscopic fluorescent signal levels (TBR) and tracer distribution observed
by NIR fluorescence imaging using the intraoperative multispectral F2 camera
system as well as the ex vivo back-table imaging;
- Macroscopic and real-time quantification of the fluorescent signal observed
by means of the MDSFR/SFF spectroscopy probe (M/m3);
- Standard histopathological assessment (i.e. hematoxylin and eosin staining)
to correlate fluorescent and non-fluorescent areas detected in vivo with
histology using in vivo obtained biopsies and surgical specimen;
- VEGF expression by means of VEGF immunohistochemistry;
Secondary outcome
- Patient characteristics (age, sex, BMI, history and morbidity, localization
and extent of SNIP, treatment outcome, blood pressure, pulse and temperature
before and after tracer administration, baseline blood count/liver and kidney
function, signs and symptoms before and after tracer administration);
- Surgical specimen histopathologic characteristics;
- Histopathologic examinations related to ex vivo VEGF expression and
bevacizumab-IRDye800CW distribution.
Background summary
During surgical resection, it is very challenging to discriminate between
sinonasal inverted papilloma (SNIP) and surrounding tissue, as SNIP is
associated with inducement of granulomatous inflammation of the environment. As
a result, the surgeon has to perform a thorough resection in order to remove
all tumor tissue, which is associated with substantial morbidity. Clearly,
there is need for an instrument that is able to guide the surgeon to
discriminate between SNIP and surrounding tissue. Molecular imaging techniques
using targeted optical contrast agents is a promising technique to accommodate
this need. Vascular Endothelial Growth Factor (VEGF) is overexpressed in SNIP
compared to normal epithelium of the sinonasal area and has been used
effectively in molecular imaging.
Study objective
The main objective is to study if the conjugate bevacizumab-IRDye800CW
accumulates more in sinonasal inverted papilloma than in normal sinonasal
mucosa, with a TBR of *2 as cutoff value.
Study design
The current study is a non-randomized, non-blinded, prospective, single center,
pilot dose-escalation study. A minimum of five and a maximum of eight patients
with SNIP will be included. Five patients will be administered with 10 mg
bevacizumab-IRDye800CW. An interim analysis is performed after inclusion of the
first three patients to determine if a tumor-to-background ratio (TBR) of *2 is
obtained by either intraoperative fluorescence in vivo measurements or by ex
vivo back-table fluorescence imaging. If a TBR of *2 is found, inclusion is
continued to five patients. If not, the dose is adjusted to 25 mg. Again, a
similar interim analysis is performed after inclusion of the first three
patients to determine the TBR.
Intervention
Patients will - after written informed consent - receive an intravenous
injection of the fluorescent tracer. Two to four days later, the fluorescence
guided surgery will be performed using a combination of the SurgVision F2
multispectral imaging system (SurgVision BV, *t Harde, the Netherlands) and a
nasopharyngeal endoscope.
Study burden and risks
Burden:
Time investment: Patients need to visit the UMCG two to four days before their
planned surgery which will take approximately two hours. Extra procedures:
1) Intravenous administration of bevacizumab-IRDye800CW.
2) The estimated time for taking fluorescence images and MDSFR-spectroscopy
measurements is approximately 15 minutes. Therefore the time under general
anesthesia will be prolonged.
3) Prior to surgical resection, biopsies are taken of fluorescent and
non-fluorescent areas, or areas of inverted papilloma and normal mucosal lining
of sinonasal cavities involved as identified by the surgeon when intraoperative
fluorescent signal is not detected.
4) Immediately after resection of the inverted papilloma, biopsies will be
taken from areas in the wound bed showing high fluorescent signal.
Risks:
Risks to study participants are mainly related to the, already present, risks
of the surgical procedure and to the administration of the tracer in increasing
dosages. A data safety monitoring board (DSMB) will not be installed as in more
than two hundred patients receiving bevacizumab-IRDye800CW, no (serious)
adverse events were observed.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
- Biopsy confirmed diagnosis of SNIP and scheduled to undergo surgical resection as decided by the Multi-Disciplinary Head and Neck Tumor Board of the UMCG;
- Age * 18 years;
- Written informed consent;
- Mentally competent person that is able and willing to comply with study procedures;
- Acceptable hematologic status, kidney function and liver function, as standard surgery protocol requires.
Exclusion criteria
- Medical or psychiatric conditions that compromise the patient*s ability to give informed consent;
- Concurrent uncontrolled medical conditions;
- Received an investigational drug within 30 days prior to the dose of the fluorescent tracer;
- Tumors at sites of which the surgeon would assess that in vivo imaging would not be feasible;
- History of myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease or unstable angina within 6 months prior to enrollment;
- Inadequately controlled hypertension with or without current antihypertensive medications;
- History of infusion reactions to bevacizumab or other monoclonal antibody therapies;
- Pregnant or lactating women. Documentation of a negative pregnancy test must be available for women of childbearing potential. Woman of childbearing potential are premenopausal women with intact reproductive organs and women less than two years after menopause;
- Lab values that in the opinion of the primary surgeon would prevent surgical resection;
- Life expectancy < 12 weeks;
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 | EUCTR2018-002519-93-NL |
| CCMO | NL66494.042.18 |