Development of a Fluorescent Visualization System for Non-visible Lung Cancer Nodules

To date, lung resection and lymphadenectomy remain the best curative option in patients with early-stage non-small cell lung cancer. Moreover, cancer screening programs have led to a frequent diagnoses of indeterminate lung lesions, many of which require surgical biopsy for diagnosis and intervention. Additionally, pre-operative imaging assessment frequently underestimates lymph-node involvement. Finally, the increase in the utilization of minimally invasive procedures remains mandatory. The aim of our project is to verify if Cetuximab-IRDye800 could detect cancer nodules and lymph node metastases during minimally invasive thoracic surgery. A result favoring the use of Cetuximab-IRDye800 would permit the use of a minimally invasive approach to a more significant number of patients, which are presently operable only by a traditional "open" approach. Consequentially, it would lead to an improvement in surgical outcomes, a reduction of costs, and an enhanced patient quality of life. In addition, a result favoring Cetuximab-IRDye800 could consent to correctly remove mislead metastatic lymph nodes (i.e., unexpected lymph-nodes metastasis) and neoplastic localization unidentified at pre-operative diagnostic assessments. It would lead to more accurate cancer staging, and a tailored post-operative treatment. Finally, the investigators expect to validate using Cetuximab-IRDye800 as an optimal tracker that can be easily applied intraoperatively during minimally invasive surgical procedures.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion criteria:

1. Clinical Stage I non-small cell lung cancer
2. \- Considered candidate to minimally invasive surgical resection after pre-operative assessment
3. Adequate organ function
4. Performance status (ECOG) ≤2
5. Potentially fertile female subjects must agree to use highly effective contraception throughout the - study and for three months after the last dose of the study medication
6. Written informed consent

Exclusion criteria:

1. Previous systemic treatments for lung cancer
2. Previous radiotherapy on lung or mediastinum
3. \- Concomitant disorders that compromise the ability to adhere to the procedures of the Protocol
4. Hemoglobin \< 9 gm/dL
5. Platelet count \< 100,000/mm³
6. Leukocyte count \< 3000/mm³
7. Absolute neutrophil count \< 1500/mm³
8. Magnesium, potassium, and calcium \< the lower limit of normal per institution normal lab values
9. Thyroid-stimulating hormone (TSH) \> 13 micro international units/mL
10. Received an investigational drug within 30 days or 5 half-life prior to the first dose of cetuximab IRDye800
11. Within 6 months prior to enrollment, myocardial infarction; cerebrovascular accident; uncontrolled congestive heart failure; significant liver disease; or unstable angina
12. History of infusion reactions to cetuximab or other monoclonal antibody therapies
13. Evidence of QT prolongation on pretreatment electrocardiogram (ECG) (greater than 440 ms in males or greater than 450 ms in females)
14. Hypersensitivity to Cetuximab-IRDye800, Cetuximab, or any of the excipients.
15. Receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents
16. Pregnancy, assessed by a pregnancy serum test (βhCG), or breastfeeding

• DERIVEDBeffa ED, Lyberis P, Rosboch GL, Arezzo A, Lococo F, Carena L, Sciorsci E, Monica V, Lausi PO, Dusi V, Busardo FP, Buffa E, Stefania R, Ciccone G, Monagheddu C, Capello BM, Vancheri R, Garrone P, Gabbarini F, Cattel F, Ruffini E, Guerrera F. Study protocol for Near-infrared molecular imaging for lung cancer detection and treatment during mini-invasive surgery (phase II Trial) - (the RECOGNISE study). BMC Cancer. 2024 Sep 2;24(1):1078. doi: 10.1186/s12885-024-12859-6. PMID 39218855