A Phase I Randomized Controlled Trial of Intratumoral Lidocaine Injection Before Transoral Robotic Surgery (TORS) and Neck Dissection for HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Summary

Based on evidence that the local anesthetic lidocaine may have anticancer effects, this study will assess the safety and efficacy of intratumoral lidocaine injection at the time of direct laryngoscopy prior to TransOral Robotic Surgery (TORS) and neck dissection for oropharyngeal squamous cell carcinoma (OPSCC). The primary objective of the study is to determine if intratumoral lidocaine injection is safe and causes a major pathologic treatment effect in the primary tumor following surgical resection. The secondary objectives will be to determine if intratumoral lidocaine injection improves locoregional control rates, progression-free survival, metastasis-free survival, and overall survival compared to no injection.

Detailed description

This is a phase I patient-blinded, randomized controlled trial evaluating intratumoral lidocaine injection prior to definitive surgery in HPV associated OPSCC. Patients with OPSCC undergoing direct laryngoscopy who are being considered for definitive TORS and selective neck dissection, will be eligible. Patients will be randomized and blinded to intratumoral injection of 1% lidocaine (intervention arm) or no injection (control arm) at the time of direct laryngoscopy. After administration of general anesthesia and biopsy, lidocaine will be injected under direct visualization (not exceeding the maximum tolerated dose of 4.5 mg/kg body weight) into the primary tumor. Blood samples will be obtained prior to direct laryngoscopy/study intervention (pre-biopsy) and again after the intervention (post-biopsy). Following direct laryngoscopy/study intervention, patients will receive institutional standard of care treatment which may include primary surgery (TORS primary site resection, selective neck dissection, and any indicated adjuvant therapy) or primary radiation (with or without chemotherapy). For patients undergoing surgery, the pathological tumor response (pTR) rate (defined as the area with pathologic response/area pathologic response plus viable tumor) will be determined by the designated study pathologist using increments of 10% for the biopsy and surgery specimens. The scores will be grouped as pTR-0 (\<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). All enrolled patients will be assessed for safety measured by adverse events. If a patient does not ultimately receive primary surgery following their direct laryngoscopy/study intervention (based on surgical candidacy, patient preference, or other reasons), then they will not be counted as an evaluable subject, as the primary endpoint pTR requires a surgical specimen for evaluation. If a patient is determined to have a pathology other than HPV associated OPSCC after their direct laryngoscopy, then they will not be counted as an evaluable subject. The enrollment target will be 30 evaluable subjects. Primary Objectives: Determine if intratumoral 1% lidocaine injection at the time of direct laryngoscopy prior to TORS and neck dissection for HPV associated OPSCC is safe and causes a major pathologic treatment effect. Secondary Objectives: Determine if intratumoral 1% lidocaine injection at the time of direct laryngoscopy prior to TORS and neck dissection for HPV associated OPSCC improves the locoregional control rates, progression-free survival, metastasis-free survival, and overall survival compared to no injection.

Arms & interventions

• DrugLidocaine 1% Injectable Solution

  1% lidocaine will be injected under direct visualization (not exceeding the maximum tolerated dose of 4.5 mg/kg body weight) into the primary tumor with the aim to distribute the lidocaine evenly into the tumor.

Outcome measures

Eligibility criteria