Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer

Study Overview
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Brief Summary
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This is a two-staged clinical trial to investigate the feasibility of intraoperative Fluorescence Imaging (FLI) to adequately assess tumor margins in patients with oral cancer using cRGD-ZW800-1.

Detailed Description
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Work package I: In WP-I, the preferred dose of the agent for imaging of margins in oral cancer will be determined. The signal-to-noise ratio will be determined in dose group A (n=7), which will receive 0.05 mg/kg of the tracer, 16-20 hours before surgery. After an interim evaluation of this ratio, the second dose group B (n=7) will receive either a higher or a lower dosage (to be determined) of the tracer. After inclusion of all patients (n=14), the dose with the highest intraoperative signal-to-noise ratio will be selected. Work package II: In WP-II, an expansion cohort (n=14) will be added to the group of patients that had received the selected dose in WP-I. In this group of 21 patients, it will be determined if FLI can improve the rate of adequate surgical resection margins. As secondary research questions, the following aspects will be assessed: sensitivity, specificity, positive and negative predictive values of FLI; colocalization with immunohistochemistry; change in surgical management; incremental operation time; FLI of excised cervical lymph nodes.

Official Title
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Guided by Light: Optimizing Surgical Excision of Oral Cancer Using Real-time Fluorescence Imaging

Conditions
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Squamous Cell Carcinoma of the Head and Neck, Oral Cancer, Squamous Cell Carcinoma of the Oral Cavity

Intervention / Treatment
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* Drug: cRGD-ZW800-1.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with biopsy-proven squamous cell carcinoma of the oral cavity, eligible for surgical resection of the primary tumor; ≥ 18 years of age; Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations; Screening ECG and clinical laboratory test results are within normal limits, or if any are outside of normal limits they are considered to be clinically insignificant. Exclusion Criteria: Previous surgery, chemotherapy or radiotherapy to the oral cavity; History of a clinically significant allergy or anaphylactic reactions to any of the components of the agent. Patients pregnant or breastfeeding, lack of effective contraception in male or female patients with reproductive potential; Patients with renal insufficiency (eGFR<60); Patients with a previous kidney transplantation in the medical history; Immuno-compromised patients who do not have the ability to respond normally to an infection due to an impaired on weakened immune system, caused by either a pre-existing disease or concomitant medications; Any condition that the investigator considers to be potentially jeopardizing the patient's well-being or the study objectives.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WP-I dose A<br>n=7. Injection of 0.05 mg/kg cRGD-ZW800-1, within 16-20 hours before imaging/surgery | Drug: cRGD-ZW800-1.<br>* Injection of cRGD-ZW800-1 within 48 hours before imaging/surgery<br>|
| Experimental: WP-I dose B<br>n=7. Injection of (to be determined) mg/kg RGD-ZW800-1, within (to be determined) hours before imaging/surgery. | Drug: cRGD-ZW800-1.<br>* Injection of cRGD-ZW800-1 within 48 hours before imaging/surgery<br>|
| Experimental: WP-II selected dose<br>n=14: expansion cohort (n=14) will be added to the group of patients that had received the selected dose in WP-I. Injection of 0.05 ór (to be determined) mg/kg cRGD-ZW800-1, within 48 hours before imaging/surgery. | Drug: cRGD-ZW800-1.<br>* Injection of cRGD-ZW800-1 within 48 hours before imaging/surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WP-I: (Highest) mean tumor-to-background ratio (TBR) | Two dosages of cRGD-ZW800-1 are tested in two groups of each 7 patients. An expansion cohort (n=14) will be added to the dose group that yields the highest TBR. | up to 48 ours post-dose | 
| WP-II: Rate of adequate (i.e. >5mm clear) tumor resection margins. |  | through histopathology, up to max 4 weeks post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WP-II: Sensitivity, specificity, positive and negative predictive values |  | through histopathology, up to max 4 weeks post-op | 
| WP-II: Co-localization of FLI with immunohistochemistry on pathology slides |  | through histopathology, up to max 4 weeks post-op | 
| WP-II: Percentage of extra tissue resection based on FLI-driven frozen sections |  | through histopathology, up to max 4 weeks post-op | 
| WP-II: Operation time |  | through histopathology, up to max 4 weeks post-op | 
| WP-II: FLI of lymph node metastases after neck dissection |  | through histopathology, up to max 4 weeks post-op | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cRGD-ZW800-1, fluorescence-guided surgery, image-guided surgery, fluorescence imaging, cancer