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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Safety measured by occurrence of adverse events.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 18 years older or more.
- •Histologically confirmed diagnosis of squamous cell carcinoma of the oropharynx or neck.
- •Clinical T1, T2, T3, or T4 stage disease of the oropharynx (per AJCC 8th Ed).
- •Any clinical N stage disease (per AJCC 8th Ed).
- •Patients must be undergoing direct laryngoscopy +/- biopsy at the University of Pennsylvania as part of their work-up for consideration of definitive TORS and selective neck dissection.
- •Patients must sign an informed consent document that indicates they are aware of the investigational nature of the treatment in this protocol as well as the potential risks and benefits.
- •Ability to understand and the willingness to provide written informed consent.
排除标准
- •Prior external beam radiation therapy to the head and neck.
- •Prior chemotherapy for head and neck cancer.
- •Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery (i.e. AJCC 7th Ed. T4b for OPSCC).
- •Presence of distant metastatic disease.
- •Uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, connective tissue disease or psychiatric illness/social situations that would limit compliance with study requirements.
- •Known history of hypersensitivity to lidocaine or other amide local anesthetics.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Lidocaine Injectible product
Intratumoral injection of 1% lidocaine at the time of direct laryngoscopy.
干预措施: Lidocaine 1% Injectable Solution (Drug)
结局指标
主要结局
Safety measured by occurrence of adverse events.
时间窗: 2 years
Adverse events (AE) and Serious Adverse Events (SAE) will use the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The CTCAE v.5 utilizes a five point scale to report AEs, defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Pathological tumor response (pTR) in the primary tumor following surgical resection.
时间窗: 2 years
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%).
次要结局
- 2-year locoregional control rates.(2 years)
- 2-year progression-free survival.(2 years)
- 2-year metastasis-free survival.(2 years)
- 2-year overall survival.(2 years)
研究者
Ryan Carey
Assistant Professor
Abramson Cancer Center at Penn Medicine