Phase II Panitumumab-IRDye800 in Head & Neck Cancer

Head and neck squamous cell carcinoma tumors can be difficult to visualize intraoperatively. Most primary oral cavity cancers and previously irradiated head and neck cancers require surgical resection for definitive treatment. Currently, tumor margins are determined intraoperatively by a combination of palpation, visual inspection, and microscopic assessment frozen tissue sections. Difficulty in assessing intraoperative tumor margins of primary head and neck cancers makes resection inexact -the incidence of involved or close surgical margins in head and neck cancer patients approaches 40% on histopathological review. Failure to obtain a complete tumor resection results in significantly worse outcomes in head and neck cancer patients. With the exception of previously untreated tongue cancers, assessment of tumor margins by intraoperative palpation is limited because tumors are adjacent to bone or cartilage (larynx), in deep structures, or in previously irradiated tissues. More accurate assessment of tumor extent could limit the ablative defect size and improve outcomes.

Intraoperative frozen sections are used to confirm complete resection of tumors. Unfortunately, these have significant deficiencies. Frozen sections 1) require resection of additional normal tissue for assessment, 2) add between 30 and 60 minutes to the operative time, 3) are difficult to interpret in patients with field cancerization or previous irradiation, 4) cannot be performed on bone or calcified cartilage, 5) are reversed on permanent section in approximately 5% of cases and 6) fail to detect close margins (> 5 mm). Finally, and perhaps most importantly, frozen sections are highly accurate if the right tissue is biopsied and sent; however, less than 5% of the wound bed can be assessed by frozen section and this significantly limits the sensitivity of this technique. This sampling error consistently plagues surgeons and pathologists alike.

Identification of margins during resection is difficult because tumors cannot be palpated and the surgeon must rely only on subtle tissue changes when using the operating microscope. Optical imaging is ideally suited to endoscopic and robotic operative approaches since the surgeon is operating from the video monitor and fluorescence can be easily incorporated into the surgeon's view. Importantly, optical imaging is being incorporated into the newest robotic platforms made especially for surgical procedures.

This is a Phase II study of panitumumab-IRDye800CW, which has emerged as the frontrunner in optical imaging. This study will be performed in the context of collaborating, completed, and ongoing dose-escalation Phase 1 clinical trials evaluating the safety of cetuximab-IRDye800 (NCT01987375) and panitumumab-IRDye800 (NCT02415881), respectively, in the same patient population. This study design is the same as our approved Phase I trials, except there will be no dose-escalation. This study design is the standard for Phase II clinical trials in the field of fluorescence-guided surgery.

The investigators saw a limited number of mild side effects with no serious side effects in patients receiving this drug (no infusion reactions, no Grade 2 or higher adverse events, and one Grade 1 adverse event in human patients). In 21% of cases, fluorescence imaging was able to improve surgical decision-making and lead to resection of tumor-containing tissue that would likely not have otherwise been resected. Given that positive margins are the single most important prognostic factor for patients with HNSCC, the potential for this technology to improve margin status has the potential to improve outcomes and survival.