Inverted PapillomaPhase 1SNIPERNCT03925285
Image Guided Surgery in Sinonasal Inverted Papilloma
A Phase 1 study testing Bevacizumab-800CW in people with Inverted Papilloma and Molecular Fluorescence Imaging, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
In sinonasal inverted papilloma (SNIP) it is very challenging to discriminate between tumor and surrounding tissue. Local recurrence is a frequent phenomenon as it occurs in 16.5% of the cases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inverted Papilloma, Molecular Fluorescence Imaging
- What is being tested?
- Bevacizumab-800CW
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteNetherlands
- Study dates
- 6 May 2019to 1 Jan 2022
- 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 SNIP and scheduled to undergo surgical resection;
- Age ≥ 18 years;
- Written informed consent;
- Mentally competent person that is able and willing to comply with study procedures.
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 bevacizumab-IRDye800CW;
- 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;
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- 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;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Image Guided Surgery in Sinonasal Inverted Papilloma by Targeting Vascular Endothelial Growth Factor
In sinonasal inverted papilloma (SNIP) it is very challenging to discriminate between tumor and surrounding tissue. Local recurrence is a frequent phenomenon as it occurs in 16.5% of the cases. There is need for an instrument that is able to guide the surgeon in removing all tumor tissue, whereas resection of healthy tissue is minimalized.
Molecular fluorescence guided surgery enables the visualization of targeted tumor-specific biomarkers by using fluorescence, thereby enhancing the contrast between normal mucosa and tumor tissue. The objective of this feasibility study is to determine if the intravenously administered conjugate bevacizumab-IRDye800CW accumulates more in SNIP than in normal sinonasal epithelium.
Read the detailed description
Rationale: 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 the complete inverted papilloma, 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.
Objectives: The main objective is to study if the conjugate bevacizumab-IRDye800CW accumulates more in sinonasal inverted papilloma than in normal sinonasal mucosa.
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.
Study population: All included patients will meet the in- and exclusion criteria and have a biopsy confirmed diagnosis of primary or recurrent sinonasal inverted papilloma and are scheduled to undergo surgical resection.
Patient related study procedures: Patients will - after written informed consent - receive an intravenous injection of the fluorescent tracer. The dose will be either 10 mg or 25 mg. Two to four days later, the peroperative fluorescence imaging and multidiameter single fiber reflectance and single fiber fluorescence (MDSFR/SFF) spectroscopy will be performed of the tumor and woundbed.
Main study parameters/endpoints are macroscopic fluorescent signal levels, tumor to background ratio (TBR) and tracer distribution observed by fluorescence imaging and quantification of the fluorescent signal observed by means of MDSFR/SFF spectroscopy. Results of fluorescence imaging and spectroscopy will be correlated with standard histopathological assessment (i.e. hematoxylin and eosin staining) and VEGF immunohistochemistry.
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/SFF spectroscopy measurements is approximately 15 minutes, which will result in prolongation of general anesthesia with 15 minutes. 3) Prior to surgical resection, the surgeon takes biopsies 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.
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
- Inverted Papilloma, Molecular Fluorescence Imaging
- Being tested
- Bevacizumab-800CW
- Medical subject headings
- Papilloma, Inverted
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab-800CWDrug
Also called Bevacizumab-IRDye800CW
Two to four days prior to surgery bevacizumab-800CW will be administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| IV fluorescent tracer bevacizumab-800CW | Experimental | Patients will be administered with 10 or 25 bevacizumab-800CW. Receives: Drug: Bevacizumab-800CW |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor-to-background ratio of mean fluorescence intensity
Measured: Up to day 4
Secondary outcomes (2)
Histopathologic assessment (H&E staining) of surgical specimen
Fluorescence signal will be correlated to histology of tissue (inverted papilloma, inflammation, malignant tumor, healthy tissue).
Measured: Approximately two weeks
VEGF immunohistochemistry of surgical specimen
VEGF immunohistochemistry to correlate fluorescence signal with VEGF quantities
Measured: Approximately two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2019
- Study start6 May 2019
- Primary completion1 Jul 2021 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inverted PapillomaStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- 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
- Single group
- Model description
- Patients are administered with bevacizumab-800CW. 2-4 days later, fluorescence imaging will be performed peroperatively
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr. M.J.H. Witjes, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03925285
- Sponsor's protocol ID
- NL66969.042.18
- Acronym
- SNIPER
- Status last verified
- Apr 2021
- First submitted
- 13 Feb 2019
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vonk J, Voskuil FJ, de Wit JG, Heeman WT, Nagengast WB, van Dam GM, Feijen RA, Korsten-Meijer A, van der Vegt B, Witjes M. Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study. Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1640-1649. doi: 10.1007/s00259-021-05567-x. Epub 2021 Nov 5.
PubMed 34738141
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Image Guided Surgery in Sinonasal Inverted Papilloma by Targeting Vascular Endothelial Growth Factor
- ClinicalTrials.gov ID
- NCT03925285
- Acronym / sponsor ID
- SNIPER / NL66969.042.18
- Conditions
- Inverted Papilloma, Molecular Fluorescence Imaging
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- 6 May 2019 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 24 Apr 2019 (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.
In sinonasal inverted papilloma (SNIP) it is very challenging to discriminate between tumor and surrounding tissue. Local recurrence is a frequent phenomenon as it occurs in 16.5% of the cases. There is need for an instrument that is able to guide the surgeon in removing all tumor tissue, whereas resection of healthy tissue is minimalized.
Molecular fluorescence guided surgery enables the visualization of targeted tumor-specific biomarkers by using fluorescence, thereby enhancing the contrast between normal mucosa and tumor tissue. The objective of this feasibility study is to determine if the intravenously administered conjugate bevacizumab-IRDye800CW accumulates more in SNIP than in normal sinonasal epithelium.
Detailed description
Rationale: 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 the complete inverted papilloma, 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.
Objectives: The main objective is to study if the conjugate bevacizumab-IRDye800CW accumulates more in sinonasal inverted papilloma than in normal sinonasal mucosa.
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.
Study population: All included patients will meet the in- and exclusion criteria and have a biopsy confirmed diagnosis of primary or recurrent sinonasal inverted papilloma and are scheduled to undergo surgical resection.
Patient related study procedures: Patients will - after written informed consent - receive an intravenous injection of the fluorescent tracer. The dose will be either 10 mg or 25 mg. Two to four days later, the peroperative fluorescence imaging and multidiameter single fiber reflectance and single fiber fluorescence (MDSFR/SFF) spectroscopy will be performed of the tumor and woundbed.
Main study parameters/endpoints are macroscopic fluorescent signal levels, tumor to background ratio (TBR) and tracer distribution observed by fluorescence imaging and quantification of the fluorescent signal observed by means of MDSFR/SFF spectroscopy. Results of fluorescence imaging and spectroscopy will be correlated with standard histopathological assessment (i.e. hematoxylin and eosin staining) and VEGF immunohistochemistry.
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/SFF spectroscopy measurements is approximately 15 minutes, which will result in prolongation of general anesthesia with 15 minutes. 3) Prior to surgical resection, the surgeon takes biopsies 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.
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
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients are administered with bevacizumab-800CW. 2-4 days later, fluorescence imaging will be performed peroperatively
| Arm | Type | Receives |
|---|---|---|
| IV fluorescent tracer bevacizumab-800CW | Experimental | Drug: Bevacizumab-800CWPatients will be administered with 10 or 25 bevacizumab-800CW. |
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 SNIP and scheduled to undergo surgical resection;
- Age ≥ 18 years;
- Written informed consent;
- Mentally competent person that is able and willing to comply with study procedures.
Key exclusion criteria (10 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 bevacizumab-IRDye800CW;
- 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;
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 |
|---|---|---|
| Bevacizumab-800CWAlso: Bevacizumab-IRDye800CWTwo to four days prior to surgery bevacizumab-800CW will be administered intravenously | Drug | IV fluorescent tracer bevacizumab-800CW |
Primary outcome
Tumor-to-background ratio of mean fluorescence intensity
Time frame: Up to day 4
2 secondary outcomes
Histopathologic assessment (H&E staining) of surgical specimen
Time frame: Approximately two weeks
VEGF immunohistochemistry of surgical specimen
Time frame: Approximately two weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Derived from this study: PubMed 34738141Vonk J, Voskuil FJ, de Wit JG, Heeman WT, Nagengast WB, van Dam GM, Feijen RA, Korsten-Meijer A, van der Vegt B, Witjes M. Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study. Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1640-1649. doi: 10.1007/s00259-021-05567-x. Epub 2021 Nov 5.
- Individual participant dataSharing planned: No
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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 Bevacizumab-800CW in people with Inverted Papilloma and Molecular Fluorescence Imaging, 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 10 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: status not confirmed, as of the sponsor's last update on 3 May 2021. 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?
Results are not available in the source record.
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?
Tumor-to-background ratio of mean fluorescence intensity (time frame: Up to day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03925285, which also lists 1 linked publication.
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 3 May 2021.