The main aim is to test whether cetuximab-IRDye800CW is a reliable marker for residual tumor remnants in resection margins after surgical removal of head and neck cancer. To increase the specificity of cetuximab-800CW, a specific frozen section can…
ID
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Macroscopic fluorescent signals on the excised tissue specimen and tracer
distribution observed with fluorescence imaging;
- Detection rates of tumor-positive margins and close margins using
fluorescence imaging and FFS;
- Number of additional resections based on the obtained fluorescent imaging and
FFS data.
Secondary outcome
- Patient characteristics (age, sex, BMI, history and morbidity, localization
of primary tumor and lymph node metastasis, vital parameters and presence of
symptoms before and after tracer administration);
- Feasibility of on-site, intra-operative, tissue analysis by both surgeon and
pathologist.
- Feasibility of novel 3D imaging methods of the obtained additional biopsies
(if clinical feasible) and correlation with standard histopathology
Background summary
Surgery remains one of the main pillars in the treatment of head and neck
cancer. Margin status is the most important predictor of local tumor control in
surgically treated head and neck cancer and determines postoperative treatment.
A margin of <1 mm of normal tissue is considered a positive margin and requires
reoperation or postoperative chemoradiation with a combination of cisplatin and
5FU, which substantially increase morbidity. Margins wider than 1 mm require
re-operation or, if that is not possible, post-operative radiotherapy without
the concomitant use of chemotherapy. This causes fewer side effects than
radiation with chemotherapy. Currently, no technology is available in the
operating room that reliably supports the surgeon during tumor excision to
assess the status margin. In fact, surgeons can only combine preoperative
imaging data with tactile and visual information during surgery to assess tumor
margins with limited accuracy. With the introduction of molecular imaging
techniques using near-infrared (NIR) fluorescent optical contrast agents
coupled to monoclonal antibodies, new avenues have been opened for
intraoperative assessment of tumor boundaries. These tracers are based on
antibodies directed against epidermal growth factor receptor, i.e.
cetuximabIRDye800CW, in patients with head and neck cancer. Initial studies
have shown that systemic administration of these compounds is safe and tumor
specific. Phase I studies, performed at the UMCG, among others, show promising
results with regard to intraoperative margin determination. These findings are
the reason to further investigate this innovative application, with the focus
on improving specificity and making it directly clinically applicable. . In
other words, to be able to act immediately on the basis of the gathered
results. The research is subsidized by the UMCG, in the context of a Mandema
Stipendium, which is awarded to young researchers (Dr. F.J. Voskuil).
Study objective
The main aim is to test whether cetuximab-IRDye800CW is a reliable marker for
residual tumor remnants in resection margins after surgical removal of head and
neck cancer. To increase the specificity of cetuximab-800CW, a specific frozen
section can be taken peroperatively, based on the fluorescence, in consultation
between the surgeon and pathologist.
The aim is to improve the positive predictive value of cetuximab-IRDye800CW
fluorescence as a marker for a tumor positive resection margin.
Study design
The study is designed as a follow-up phase 2 study, a prospective
cross-sectional diagnostic study in patients with head and neck cancer
requiring surgical excision.
This study is a follow-up to an already performed study in which patients with
head and neck cancer (n=80) were administered the fluorescent substance
cetuximab-800CW, and the optimal dose of this substance was determined (75mg
cetuximab followed by 15mg cetuximab-800CW). ). This study showed that
cetuximab-800CW has an excellent sensitivity for cancer detection in the
margin, but the specificity can still be improved. The present study attempts
to improve this by specifically taking a frozen section of the margin on the
excised tissue specimen, based on the fluorescence imaging. Based on this
finding, an additional resection can be performed immediately if deemed useful
and safe by the surgeon. This follow-up study will serve as a prelude to a
multicenter phase III study. In the current study 20 patients will be included.
Intervention
Tracer administration: patients visit the hospital 2 days prior to their
scheduled surgery for their head and neck tumor.
The cetuximab-IRDye800CW will be injected by slow infusion and patients will be
monitored for potential
effects. Patients receive unlabeled dose of cetuximab (75mg) 1 hour prior to
15mg
Received cetuximab-irdy800cw. Before cetuximab administration, 2mg clemastine
will be administered, according to standard protocol cetuximab administration
in the UMCG.
If, on the basis of fluorescence imaging and/or frozen section determination,
it is considered useful and safe to perform a direct resection in order to
achieve a wide margin, this can be performed peroperatively.
Study burden and risks
Burden - Time investment: Patients have to make an extra visit to the UMCG, two
days before their planned surgery, which takes about 2-3 hours. Usually
patients are admitted one day before the scheduled surgery. Burden of
additional procedures: 1) Intravenous administration of cetuximab-IRDye800CW
and cetuximab. 2) Estimated time for taking fluorescence images is
approximately 10-15min. However, the surgery often does not have to wait for
this, as other actions can be performed while performing imaging of the excised
tissue. Therefore, the time under general anesthesia might be prololonged with
10-15minutes. The usual time of surgical procedures to remove head and neck
tumors ranges from 2 hours to 15 hours, depending on the complexity of the
surgical procedure. 3) If fluorescence is observed in the resection specimen,
re-resection will be considered if deemed safe by surgeon. Risks: Allergic
reactions to cetuximab have been reported, but this is considered a low risk
Benefit: Patients may benefit directly from this study. The operation will be
scheduled as usual. If fluorescence is observed in the resection specimen,
re-resection will be considered if deemed safe by surgeon. The results of this
type of research may benefit other patients with cancer in the future. Clinical
experience will be gained with fluorescent labeled antibody to assess margin
during head and neck cancer surgery.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Cytology and/or histology-confirmed diagnosis of oral squamous cell carcinoma
and scheduled to undergo surgical removal as decided by the multidisciplinary
head and neck tumor board of the UMCG;
- Age >= 18 years;
- Written informed consent.
Exclusion criteria
- Medical or psychiatric conditions that compromise the patient*s ability to
give informed consent;
- Concurrent uncontrolled medical conditions;
- Participated in a clinical trial in which an investigational drug was
administrated within 30 days prior to the dose of cetuximab-800CW;
- History of myocardial infarction, cerebrovascular accident, uncontrolled
cardiac heart failure, significant liver disease (ALT >3X upper limits of
normal or increased total bilirubin) or unstable angina within 6 months prior
to enrollment;
- Inadequately controlled hypertension with or without current antihypertensive
medications;
- History of allergy or infusion reactions cetuximab or other monoclonal
antibody therapies;
- Pregnant or lactating women. Documentation of a negative pregnancy test must
be available for women of childbearing potential. Moreover, the need to be
willing to ensure that she or her partner uses effective contraception during
the trial and for 6 months thereafter. Woman of childbearing potential are
premenopausal women with intact reproductive organs and women less than two
years after menopause;
- Evidence of QT prolongation on pretreatment ECG (greater than 440 ms in males
or greater than 450 ms in females)
- Patients receiving Class IA (quinidine, procainamide) or Class III
(dofetilide, amiodarone, sotalol) antiarrhythmic agents.
- Life expectancy < 12 weeks;
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 | EUCTR2022-002779-12-NL |
| ClinicalTrials.gov | NCT05499065 |
| CCMO | NL81321.042.22 |