Penile CancerPhase 1GLANSNCT05376202
Image Guided Penile Cancer Surgery
A Phase 1 study testing Cetuximab-IRDye800CW in people with Penile Cancer and Margin Assessment, run by University Medical Center Groningen at 1 site in Netherlands.
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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Penile Cancer, Margin Assessment
- What is being tested?
- Cetuximab-IRDye800CW
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Mar 2022to 14 Apr 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Age ≥ 18 years
- Written informed consent
- Adequate potential for follow-up
Who cannot join
- 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 cetuximab-800CW
- Tumors at sites of which the surgeon would assess that in vivo imaging would not be feasible
- Had within 6 months prior to enrollment: myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease, unstable angina
- Inadequately controlled hypertension with or without current antihypertensive medications
Show all 13Show fewer
- History of infusion reactions to cetuximab or other monoclonal antibody therapies
- Evidence of QT prolongation on pretreatment ECG (greater than 440 ms in males or greater than 450 ms in females)
- Lab values that in the opinion of the primary surgeon would prevent surgical resection
- Patients receiving Class Ia (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
- Magnesium, potassium and calcium deviations that might lead to cardiac rhythm (grade II or higher deviations by CTCAE)
- Life expectancy < 12 weeks
- Karnofsky performance status < 70%
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fluorescent Guided Surgery in Penile Carcinoma Using Cetuximab-800IRDyeCW
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).
Read the detailed 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.
- Conditions
- Penile Cancer, Margin Assessment
- Being tested
- Cetuximab-IRDye800CW
- Medical subject headings
- Penile Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cetuximab-IRDye800CWDrug
Patients will receive 75mg Cetuximab followed by 15mg Cetuximab-IRDye800CW two days prior to surgery
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: 75mg Cetuximab and 15mg Cetuximab-IRDye800CW | Experimental | Patients receive 75mg of Cetuximab, followed by 15mg Cetuximab-IRDye800CW I.V. two days prior to surgery. Receives: Drug: Cetuximab-IRDye800CW |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Compare the spot to background ratio for tumor positive and tumor negative margins.
The main purpose is to establish the intraoperative use of cetuximab-800CW as a reliable marker for residual tumor in resection margins after surgical removal of PSCC. The objective is to establish the feasibility of cetuximab-800CW fluorescence at the dose of 75/15 mg predose/dose combination as a marker for a tumor positive resection by comparing the spot to background ratios for tumor positive and tumor negative margins. A tumor to background ratio of >2.0 is aspired.
Measured: 2 years
Secondary outcomes (1)
Quantification of sensitivity and positive predictive value of cetuximab-800CW in PSCC
To quantify sensitivity and positive predictive value of cetuximab-800CW fluorescence of PSCC ex vivo using optical molecular imaging and MDSFR/SFF versus standard immunohistochemistry.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start7 Mar 2022
- Primary completion1 May 2023
- Study completion14 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Penile CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center
- Responsible party
- Principal investigator, Max J.H. Witjes, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05376202
- Sponsor's protocol ID
- 202000333
- Acronym
- GLANS
- Status last verified
- Apr 2024
- First submitted
- 19 Apr 2022
- Last updated
- 19 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluorescent Guided Surgery in Penile Carcinoma Using Cetuximab-800IRDyeCW
- ClinicalTrials.gov ID
- NCT05376202
- Acronym / sponsor ID
- GLANS / 202000333
- Conditions
- Penile Cancer, Margin Assessment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Erasmus Medical Center
- Study start
- 7 Mar 2022 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 14 Apr 2024 (actual)
- First posted
- 17 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1: 75mg Cetuximab and 15mg Cetuximab-IRDye800CW | Experimental | Drug: Cetuximab-IRDye800CWPatients receive 75mg of Cetuximab, followed by 15mg Cetuximab-IRDye800CW I.V. two days prior to surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- Age ≥ 18 years
- Written informed consent
- Adequate potential for follow-up
Key exclusion criteria (13 listed)
- 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 cetuximab-800CW
- Tumors at sites of which the surgeon would assess that in vivo imaging would not be feasible
- Had within 6 months prior to enrollment: myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease, unstable angina
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cetuximab-IRDye800CWPatients will receive 75mg Cetuximab followed by 15mg Cetuximab-IRDye800CW two days prior to surgery | Drug | Phase 1: 75mg Cetuximab and 15mg Cetuximab-IRDye800CW |
Primary outcome
Phase 1: Compare the spot to background ratio for tumor positive and tumor negative margins.
Time frame: 2 years
The main purpose is to establish the intraoperative use of cetuximab-800CW as a reliable marker for residual tumor in resection margins after surgical removal of PSCC. The objective is to establish the feasibility of cetuximab-800CW fluorescence at the dose of 75/15 mg predose/dose combination as a marker for a tumor positive resection by comparing the spot to background ratios for tumor positive and tumor negative margins. A tumor to background ratio of >2.0 is aspired.
1 secondary outcome
Quantification of sensitivity and positive predictive value of cetuximab-800CW in PSCC
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cetuximab-IRDye800CW in people with Penile Cancer and Margin Assessment, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Compare the spot to background ratio for tumor positive and tumor negative margins. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.