Intratympanic N-Acetylcysteine (NAC) Injections for Prevention of Cisplatin-induced Ototoxicity in Head and Neck Cancer Patients: A Multi-centre Phase II Randomized Controlled Trial.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Determination of a safe and tolerable dosage for intratympanic NAC injection
研究概览
简要总结
Although many intratympanic agents have been attempted, N-Acetylcysteine (NAC) appears to be the most promising and is a powerful, commonly used anti-oxidant. The goal of this prospective phase 2 randomized controlled trial is to determine the optimal dosage and effectiveness of intratympanic NAC injection in reducing hearing loss in head & neck cancer patients receiving cisplatin chemotherapy with curative intent.
详细描述
A prospective randomized controlled trial phase 1 using a standard 3+3 design, followed by a randomized controlled phase 2 to determine dosage, safety, and efficacy of intratympanic NAC to treat hearing loss in head & neck patients receiving high-dose cisplatin chemotherapy. Participants will complete various pre-treatment hearing tests. One ear will be randomly chosen for the experimental treatment and the other ear will serve as the control ear. Participants will receive intratympanic NAC injections 60 minutes prior to their scheduled chemotherapy sessions in the experimental ear. The control ear will not receive any injection. Follow up hearing tests will be performed 2 months following completion of their primary cancer treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
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
- •Advanced stage head and neck cancer
- •Receiving high dose systemic cisplatin (100mg/m2) with concurrent radiation therapy as part of their curative intent treatment
- •Willing to provide informed consent
- •ECOG performance status 0-2
- •Histological confirmation of squamous cell carcinoma
排除标准
- •Age less than 18
- •Metastatic disease
- •Tympanic membrane perforation or the presence of tympanostomy tubes as this may impact the retention and absorption of NAC when inserted into the middle ear
- •Preexisting severe to profound sensorineural hearing loss (unilateral or bilateral)
- •Pretreatment interaural discrepancy of greater than 10dB at three frequencies
- •History of Meniere's or fluctuating hearing loss
- •Previous hypersensitivity to NAC
- •Patient unable to follow the protocol for any reason
研究组 & 干预措施
Experimental arm with Intratympanic NAC injection
One ear will be randomly chosen for the experimental treatment and receive intratympanic NAC injections 60 minutes prior to their scheduled chemotherapy sessions
干预措施: N-Acetyl Cysteine (Drug)
结局指标
主要结局
Determination of a safe and tolerable dosage for intratympanic NAC injection
时间窗: Within 1 day
The primary end-point of the phase 1 part of this study is the safety and tolerability of intratympanic NAC injections, by determining the causality of adverse events and serious adverse events and grading according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
Improvement in hearing threshold with intratympanic NAC injection
时间窗: Within 2 months
The primary outcome measure of this study will be a comparison of hearing loss between the control and NAC-injected ears. More specifically, each ear will be scored as having hearing loss if there is a greater than 10dB hearing loss in three contiguous frequencies. This will be measured via threshold hearing tests.
次要结局
- Improvement in hearing quality with intratympanic NAC injection(Within 2 months)
研究者
Dr. Trung Le
Trung N. Le MD PhD
Sunnybrook Health Sciences Centre