Evaluation of IRDye800CW-nimotuzumab in Lung Cancer Surgery

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, optimal dose and imaging time of the investigational product, IRDye800CW-nimotuzumab for use as a near infrared imaging probe for image-guided surgery during lung cancer resection. IRDye800CW-nimotuzumab targets cancer cells over-expressing EGFR, allowing tumors to be visualized and may help surgeons better identify cancer during surgery.

Official Title
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Evaluation of IRDye800CW-nimotuzumab in Lung Cancer Surgery

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: IRDye800CW-nimotuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surgically resectable Stage I and II non-small cell lung cancer Able to give informed consent Age ≥ 18 and ≤ 80 years old Adequate cardiopulmonary reserve to undergo lung resection as determined by operating surgeon No prior history of malignancy No neoadjuvant therapy Karnofsky performance status of at least 70% or Eastern Cooperative Oncology Group (ECOG)/Zubrod level 0-2 Hemoglobin (hgb) ≥ 90 g/L White blood cell count (WBC) > 3 x 109/L Platelet count (plt) ≥ 100 x 109/L Serum creatinine ≤ 1.5 times upper reference range Exclusion Criteria: Received anti-EGFR antibody therapy (cetuximab, panitumumab, necitumumab) within 60 days prior to trial drug Pregnant or nursing Known history of hypersensitivities or allergic reactions to antibodies or NSO derived products Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment Subjects receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents Subjects with a history or evidence of interstitial pneumonitis or pulmonary fibrosis Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Single center, open-label, phase I/II image-guided surgery study to assess the image quality of IRDye800CW-nimotuzumab during surgery
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose intermediate time<br>Participants will receive an i.v. infusion of 50 mg IRDye800CW-nimotuzumab. Participants will undergo lung cancer resection surgery 4-6 days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration | Drug: IRDye800CW-nimotuzumab<br>* 50 mg of IRDye800CW-nimotuzumab will be infused intravenously over a period of 30 minutes. Lung cancer resection surgery will be done at different time points post infusion<br>|
| Experimental: High dose intermediate time<br>Participants will receive an i.v. infusion of 100 mg IRDye800CW-nimotuzumab. Participants will undergo lung cancer resection surgery 4-6 days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration | Drug: IRDye800CW-nimotuzumab<br>* 50 mg of IRDye800CW-nimotuzumab will be infused intravenously over a period of 30 minutes. Lung cancer resection surgery will be done at different time points post infusion<br>|
| Experimental: Optimal dose early time<br>Participants will receive an i.v. infusion of 50 or 100 mg IRDye800CW-nimotuzumab (depending on results from cohorts 1 and 2). Participants will undergo lung cancer resection surgery 1-3 days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration | Drug: IRDye800CW-nimotuzumab<br>* 50 mg of IRDye800CW-nimotuzumab will be infused intravenously over a period of 30 minutes. Lung cancer resection surgery will be done at different time points post infusion<br>|
| Experimental: Optimal dose late time<br>Participants will receive an i.v. infusion of 50 or 100 mg IRDye800CW-nimotuzumab (depending on cohorts 1 and 2). Participants will undergo lung cancer resection surgery 7+ days after infusion. Vitals, blood sample and urine sample will be collected before infusion for a baseline. Blood and vitals will be taken post infusion. Blood and urine samples will be collected on the day of surgery. Participants will be followed up for any adverse event until day 30 post administration | Drug: IRDye800CW-nimotuzumab<br>* 50 mg of IRDye800CW-nimotuzumab will be infused intravenously over a period of 30 minutes. Lung cancer resection surgery will be done at different time points post infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Optimal dose of IRDye800CW-nimotuzumab for image guided surgery. | To identify the dose with the highest tumor fluorescence and TBR. | up to 14 days | 
| Phase 2: Determine the optimal time for IRDye800CW-nimotuzumab infusion for image guided surgery. | To identify the imaging time with the highest tumor fluorescence and TBR. | up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine primary tumor margins. | Determine the level of fluorescence that can discriminate between EGFR positive tumor tissue and normal tissue. | up to 14 days | 
| Identify EGFR positive lymph nodes. | Determine the level of fluorescence that can discriminate between EGFR positive lymph nodes and normal tissue. | up to 14 days | 
| Safety of IRDye800CW-nimotuzumab | a. Safety will be determined by recording the number of grade 2 or higher adverse events determined to be clinically significant, which are definitely, probably, or possibly related to IRDye800CW-nimotuzumab within 30 days of administration. | up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IRDye800CW, Nimotuzumab, Lung cancer, EGFR, Near infrared, Image guided surgery, Optical imaging