The purpose of the current study is to determine the feasibility of using MFGS using Cetuximab-800CW as an intraoperative margin assessment tool for penile carcinoma.
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main objective of this feasibility study is to investigate whether
cetuximab-800CW could be used for margin assessment during surgery in patients
with PSCC.
Secondary outcome
Not applicable
Background summary
The main treatment modality for Penile Squamous Cell Carcinoma (PSCC) is
surgery with curative intent. There is no difference in mortality between organ
sparing surgery and radical surgery, and for optimal cosmetic and functional
results small resection (3-5mm) margins are used. In organ sparing surgery a
tumor-positive margin of up to 36% exist. Tumor-positive surgical margins are
an independent risk factor for local recurrence, which has been reported to be
up to 18%. These local remaining tumor depositions can be continuous or
discontinuous from the main tumor, which makes it hard for the treating surgeon
to recognize them clinically. Tumor-positive margins always lead to extra,
penile sparing surgery, which leads to longer hospitalization, higher exposure
to anesthetic interventions and a worse psychological outcome.
Currently, no intraoperative imaging technique that provides real time feedback
for resection margins exists in PSCC. Molecular fluorescence-guided Surgery
(MFGS) using targeted near-infrared (NIR) optical contrast agents like for
example Cetuximab-800CW is a promising technique to accommodate this need.
Epidermal Growth Factor Receptor (EGFR) is overexpressed in PSCC and has safely
and successfully been used as target for molecular imaging, particularly for
assessment for tumor margins in head and neck squamous cell carcinoma.
Study objective
The purpose of the current study is to determine the feasibility of using MFGS
using Cetuximab-800CW as an intraoperative margin assessment tool for penile
carcinoma.
Study design
The study is a single-center prospective, phase1 feasibility study. In total,
fifteen patients with biopsy proven PSCC will be included. 2 days before
surgery, a predose of 75mg *cold* cetuximab will be administered intravenously,
followed by 15mg of cetuximab-800CW intravenously, with 1 hour between start of
the cold dose and the cetuximab-800CW. After 3 patients are included, an
interim analysis will be performed. If a tumor to background of >2 is obtained
by ex-vivo analysis, the next 12 patients will be included. If a TBR of <2 is
reached, the dose of cetuximab-800CW will be increased to 25mg with the same
predosing scheme, 75mg of cold cetuximab. When 3 patients are included second
dose, a second interim analysis will be performed. If a tumor to background of
>2 is obtained by ex-vivo analysis, 12 patients more will be included. If not,
another dose of cetuximab-800CW will be used and another interim analysis will
be performed after 3 patients.
Intervention
After written informed consent is obtained, patients will receive an
intravenous administration of 75mg *cold* cetuximab followed by 15mg of
cetuximab-800CW 1 hour after the administration of the predose. Two days after
the injection of the imaging agent, fluorescence imaging is performed
intraoperatively, both in vivo and ex vivo. 1 day after surgery, fluorescence
imaging will again be performed during pathological processing on the excised
tissue. Both intraoperatively and during the pathology process, fluorescence
will be quantified by MDSFR/SFF spectroscopy.
Study burden and risks
Burden:
The extra burden the patients associated with the study procedure is an extra
visit to the hospital 2 days before surgery for the administration of
cetuximab-800CW. This will take approximately 2 hours. Also, the surgical
procedure will be prolonged 15-20 minutes due to fluorescence imaging and
spectroscopy measurements.
Risks:
Risks to study participants are mainly related to the risks of the
administration of the imaging agent. No preclinical or clinical study reported
higher than grade 2 adverse events using cetuximab-800CW, moreover, these
studies used significant higher doses of the investigational product. Previous
studies with cetuximab-800CW reported no imaging agent related serious events.
Currently, a phase 2 trial is performed at the UMCG with Cetuximab-800CW
(NCT03134846), no grade 2 or higher imaging agent 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 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
1. Biopsy confirmed diagnosis of primary or recurrent PSCC and scheduled to
undergo surgical resection of primary or recurrent tumor with or without
(sentinel) lymph node procedure as decided by the Urology Department of the
UMCG.
2. Age >= 18 years
3. Written informed consent
4. Adequate potential for follow-up
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-800CW
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. Lab values that in the opinion of the primary surgeon would prevent surgical
resection
10. Patients receiving Class Ia (quinidine, procainamide) or Class III
(dofetilide, amiodarone, sotalol) antiarrhythmic agents
11. Magnesium, potassium and calcium deviations that might lead to cardiac
rhythm (grade II or higher deviations by CTCAE)
12. Life expectancy < 12 weeks
13. 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 | EUCTR2020-002624-37-NL |
| CCMO | NL74185.042.20 |