search
Back to results

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

Primary Purpose

Ototoxic Hearing Loss

Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
N-Acetyl Cysteine
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ototoxic Hearing Loss focused on measuring Hearing Loss, Deafness, Cisplatin-induced Ototoxicity, Sensorineural hearing loss, Ear diseases, Antioxidant, N-acetyl cystein

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Odette Cancer Centre, Sunnybrook Health Sciences CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Experimental arm with Intratympanic NAC injection

Control arm with No injection

Arm Description

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

The control ear will not receive any injections

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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.

Full Information

First Posted
February 26, 2020
Last Updated
September 5, 2023
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Toronto Sunnybrook Regional Cancer Centre, London Regional Cancer Program, Canada
search

1. Study Identification

Unique Protocol Identification Number
NCT04291209
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 26, 2020 (Actual)
Primary Completion Date
May 1, 2024 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Toronto Sunnybrook Regional Cancer Centre, London Regional Cancer Program, Canada

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ototoxic Hearing Loss
Keywords
Hearing Loss, Deafness, Cisplatin-induced Ototoxicity, Sensorineural hearing loss, Ear diseases, Antioxidant, N-acetyl cystein

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental arm with Intratympanic NAC injection
Arm Type
Active Comparator
Arm Description
One ear will be randomly chosen for the experimental treatment and receive intratympanic NAC injections 60 minutes prior to their scheduled chemotherapy sessions
Arm Title
Control arm with No injection
Arm Type
No Intervention
Arm Description
The control ear will not receive any injections
Intervention Type
Drug
Intervention Name(s)
N-Acetyl Cysteine
Other Intervention Name(s)
NAC
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determination of a safe and tolerable dosage for intratympanic NAC injection
Description
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
Time Frame
Within 1 day
Title
Improvement in hearing threshold with intratympanic NAC injection
Description
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.
Time Frame
Within 2 months
Secondary Outcome Measure Information:
Title
Improvement in hearing quality with intratympanic NAC injection
Description
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.
Time Frame
Within 2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Varia Sajeniouk
Phone
1-416-480-6100
Ext
85392
Email
varia.sajeniouk@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Trung N Le
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Odette Cancer Centre, Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Varia Sajeniouk
Phone
1-416-480-6100
Ext
85392
Email
varia.sajeniouk@sunnybrook.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs