Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05376202 |
Other study ID # |
202000333 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
March 7, 2022 |
Est. completion date |
April 14, 2024 |
Study information
Verified date |
April 2024 |
Source |
University Medical Center Groningen |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The main treatment modality for Penile Squamous Cell Carcinoma (PSCC) is surgery with
curative intent. 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%. 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 (ICON
study, UMCG1).
Description:
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 (ICON
study, UMCG1).
Objectives:
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. 2-4 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 with either in vivo or 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 in the second
dose group, 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 a TBR of <2 is found, the
study will be terminated.
Study population:
Patients with histologically proven PSCC who meet all in- and exclusion criteria, and are
opted for primary surgery as their treatment.
Patient related study procedures:
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. 2-4 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.
Main study parameters/endpoints:
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.
Burden, risks and benefit related to participation.
Burden:
The extra burden the patients associated with the study procedure is an extra visit to the
hospital 2-4 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.