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

Sponsor

Sunnybrook Health Sciences Centre (Other)

Overall Status

Recruiting

CT.gov ID

NCT04291209

Collaborator

Toronto Sunnybrook Regional Cancer Centre (Other), London Regional Cancer Program, Canada (Other)

Enrollment

Location

Arms

42.2

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ototoxic Hearing Loss	Drug: N-Acetyl Cysteine	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

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.

Actual Study Start Date :

Feb 26, 2020

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	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. Other Names: NAC
No Intervention: Control arm with No injection The control ear will not receive any injections

Arm

Intervention/Treatment

Active Comparator: 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

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.

Other Names:

NAC

No Intervention: Control arm with No injection

The control ear will not receive any injections

Outcome Measures

Primary Outcome Measures

Determination of a safe and tolerable dosage for intratympanic NAC injection [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 [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.

Secondary Outcome Measures

Improvement in hearing quality with intratympanic NAC injection [Within 2 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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