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

September 5, 2023 updated by: Dr. Trung Le, Sunnybrook Health Sciences Centre

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Odette Cancer Centre, Sunnybrook Health Sciences Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of a safe and tolerable dosage for intratympanic NAC injection
Time Frame: 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
Within 1 day
Improvement in hearing threshold with intratympanic NAC injection
Time Frame: 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.
Within 2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in hearing quality with intratympanic NAC injection
Time Frame: 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.
Within 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

London Regional Cancer Program, Canada
Toronto Sunnybrook Regional Cancer Centre

Investigators

  • Principal Investigator: Trung N Le, Sunnybrook Health Sciences Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2020

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

May 1, 2024

Study Registration Dates

First Submitted

February 26, 2020

First Submitted That Met QC Criteria

February 27, 2020

First Posted (Actual)

March 2, 2020

Study Record Updates

Last Update Posted (Estimated)

September 6, 2023

Last Update Submitted That Met QC Criteria

September 5, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1819 (Other)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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