Intratympanic N-Acetylcysteine for Prevention of Cisplatin-induced Ototoxicity.

Sunnybrook Health Sciences Centre

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Ototoxic Hearing Loss

Treatments: Drug: N-Acetyl Cysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT04291209

1819 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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80 participants in 2 patient groups

Experimental arm with Intratympanic NAC injection

Active Comparator group

Description:

One ear will be randomly chosen for the experimental treatment and receive intratympanic NAC injections 60 minutes prior to their scheduled chemotherapy sessions

Treatment:

Drug: N-Acetyl Cysteine

Control arm with No injection

No Intervention group

Description:

The control ear will not receive any injections