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

Ototoxic Hearing Loss Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04291209
• Other study ID #: 1819
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 26, 2020
• Est. completion date: May 1, 2024

Study information

• Verified date: September 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: Varia Sajeniouk
• Phone: 1-416-480-6100
• Email: varia.sajeniouk[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Ototoxic Hearing Loss
• Ototoxicity

Intervention

Drug:
• N-Acetyl Cysteine
One ear will be randomly chosen for the experimental treatment of intratympanic NAC. The other ear will serve as the control ear which will not receive any injection.

Locations

Country	Name	City	State
Canada	Odette Cancer Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	London Regional Cancer Program, Canada, Toronto Sunnybrook Regional Cancer Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of a safe and tolerable dosage for intratympanic NAC injection	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	Within 1 day
Primary	Improvement in hearing threshold with intratympanic NAC injection	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.	Within 2 months
Secondary	Improvement in hearing quality with intratympanic NAC injection	The secondary outcome measure of this study will be a comparison of hearing discrimination, subjective tinnitus, otoacoustic emission, speech spatial and quality of hearing between the control and NAC-injected ears.	Within 2 months