The main purpose of this pilot study is to investigate the feasibility of fluorescence imaging using cetuximab-IRDye800CW for intraoperative margin assessment in patients with cutaneous squamous cell carcinoma.
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
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 in vivo imaging as well as
the ex vivo back-table imaging;
- Quantification of fluorescent signals using MDSFR/SFF spectroscopy;
- Standard histopathological assessment (i.e. haematoxylin and eosin staining)
to correlate fluorescent and non-fluorescent areas detected in vivo with
histology using surgical specimen;
Secondary outcome
- Patient characteristics (age, sex, BMI, history and morbidity, localization
and classification of cancer, treatment outcome, blood pressure, pulse and
temperature before and after tracer administration, signs and symptoms before
and after tracer administration).
- Histopathologic examinations related to ex vivo EGFR expression and
cetuximab-IRDyeCW800 distribution.
- Quantification of the cetuximab-800CW optoacoustic signal and the tracer
distribution observed by multispectral optoacoustic imaging using the MSOT
Acuity Echo in vivo.
Background summary
The gold standard of treatment in non-melanoma skin cancer (NMSC) is wide
surgical excision. During surgery, it is hard to discriminate between tumor and
normal tissue using visual and tactile information. Even with the use of
perioperative fresh frozen sections, there is a significant risk of a
tumor-positive margin post-operatively. Micrographic surgery techniques have
been developed to ensure the complete removal of tumor tissue, while maximizing
normal tissue conservation. Mohs Micrographic Surgery (MMS) is recommended for
high-risk and recurrent basal cell carcinoma, cutaneous squamous cell carcinoma
(cSCC) and other uncommon skin tumors (1). In MMS, surgical mapping is used
during resection of the tumor: the surgeon removes the lesion, directly
followed by 100% histological evaluation of the tumor margins on frozen
sections, in contrast to standard excision, in which only a small portion of
the margins are evaluated (2). Although MMS is beneficial for precise margin
assessment, it is time consuming and labor-intensive. The preparation usually
takes 20 to 60 minutes per excision, during which the patient waits, and the
entire cycle is repeated until a tumor free plane resection margin is achieved
(3). Moreover, the size of the tumor limits the indication for MMS. There is
need for an instrument that can reliably support tumor excision with 100%
margin control in a *real-time* manner, irrespectively to the size and origin
of the tumor.
Molecular imaging using targeted near-infrared (NIR) optical contrast agents is
a promising technique to accommodate this need. Epidermal Growth Factor
Receptor (EGFR) is overexpressed in cSCC and has successfully been used as
target for molecular imaging, particularly for assessment for tumor margins in
head and neck squamous cell carcinoma (NCT03134846, the ICON study, UMCG).
Study objective
The main purpose of this pilot study is to investigate the feasibility of
fluorescence imaging using cetuximab-IRDye800CW for intraoperative margin
assessment in patients with cutaneous squamous cell carcinoma.
Study design
The current study is a single center, prospective, cross-sectional, phase I
feasibility study. Ten patients with cSCC will be included. Two to four days
prior to surgery, patients are administered with a predose of 75 mg *cold*
cetuximab and 15 mg of the fluorescent tracercetuximab-IRDye800CW
intravenously. After inclusion five patients, an interim analysis is performed
to determine if a tumor-to-background ratio of >2 is obtained by either
intraoperative fluorescence in vivo imaging or ex vivo fluorescence imaging. If
a TBR of >2 is found, inclusion will be continued to ten patients. If not, the
dose is adjusted to a predose of 75 mg cetuximab and 25 mg of the fluorescent
tracer cetuximab-IRDye800CW and ten more patients are included.
Intervention
Patients will * after written informed consent * receive an intravenous
injection of the predose unlabeled cetuximab (after clemastine administration)
and one hour later the fluorescent tracer Cetuximab-IRDye800CW. Two to four
days later, fluorescence imaging is performed during surgery and directly after
surgery, at the department of Pathology. Furthermore, fluorescence will be
quantified by MDSFR/SFF spectroscopy. If the tumor location allows for plain
imaging with our imaging probe, optoacoustic imaging will be performed prior to
tumor resection.
Study burden and risks
Burden:
The burden associated with participation consists of one extra visit to the
hospital for tracer administration, which will take approximately 2 hours. Also
the surgical procedure and time under general anaesthesia will be prolonged
with approximately 15-30 minutes for taking fluorescence images and
spectroscopy measurements. If optoacoustic imaging is performed, this will take
5 minutes maximum.
Risks:
Risks to study participants are mainly related to the, already present, risks
of the surgical procedure and to the administration of the tracer. No
preclinical or clinical study reported higher than grade 2 adverse events,
moreover, these studies used significant higher doses of the investigational
product. Previous studies with cetuximab-IRDye800CW reported no tracer related
serious events. Currently, a phase 1-2 trial is performed at the UMCG with
Cetuximab-IRDye800 (NCT03134846), no tracer related serious advents were
reported so far.
Benefit:
Patients will have no benefit from this study directly. Surgery will be planned
as usual. During surgery, no decisions will be made based on the fluorescence
imaging.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1) Biopsy confirmed diagnosis of cSCC and scheduled to undergo surgical
resection;
2) Age * 18 years;
3) Written informed consent;
4) Mentally competent person showing adequate potential for follow-up; For
female subjects who are of childbearing potential, are premenopausal with
intact reproductive organs or are less than 2 years post-menopausal:
5) A negative serum or urine pregnancy test prior to receiving the tracer.
6) 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) Concurrent uncontrolled medical conditions.
3) Received an investigational drug within 30 days prior to the dose of
cetuximab-IRDye800CW;
4) Tumors at sites of which the surgeon would assess that in vivo imaging would
not be feasible;
5) Had within 6 months prior to enrollment: myocardial infarction,
cerebrovascular accident, uncontrolled cardiac heart failure, significant liver
disease, unstable angina;
6) Inadequately controlled hypertension with or without current
antihypertensive medications;
7) History of infusion reactions to cetuximab or other monoclonal antibody
therapies
8) Evidence of QT prolongation on pretreatment ECG (greater than 440 ms in
males or greater than 450 ms in females);
9) Patients receiving Class IA (quinidine, procainamide) or Class III
(dofetilide, amiodarone, sotalol) antiarrhythmic agents;
10) Magnesium, potassium and calcium deviations that might lead to cardiac
rhythm (grade II or higher deviations by CTCAE).
11) Life expectancy < 26 weeks;
12) Karnofsky performance status < 70%.
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 | EUCTR2017-002249-31-NL |
| CCMO | NL69222.042.19 |