Clinical trial NCT04291209: Intratympanic N-Acetylcysteine for Prevention of Cisplatin-induced Ototoxicity.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Ototoxic Hearing Loss
Keywords: Hearing Loss
Deafness
Cisplatin-induced Ototoxicity
Sensorineural hearing loss
Ear diseases
Antioxidant
N-acetyl cystein
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Toronto Sunnybrook Regional Cancer Centre
name: London Regional Cancer Program, Canada
First posted: 2020-03-02
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Determination of a safe and tolerable dosage for intratympanic NAC injection
timeFrame: Within 1 day
measure: Improvement in hearing threshold with intratympanic NAC injection
timeFrame: Within 2 months
Secondary outcomes:
measure: Improvement in hearing quality with intratympanic NAC injection
timeFrame: Within 2 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Odette Cancer Centre, Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Trung N Le
role: PRINCIPAL_INVESTIGATOR
References: