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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04291209
Recruitment Status : Recruiting
First Posted : March 2, 2020
Last Update Posted : March 2, 2020
Sponsor:
Collaborators:
Toronto Sunnybrook Regional Cancer Centre
London Regional Cancer Program, Canada
Information provided by (Responsible Party):
Dr. Trung Le, Sunnybrook Health Sciences Centre

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 26, 2020
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine


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 Name: NAC

No Intervention: Control arm with No injection
The control ear will not receive any injections



Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04291209


Contacts
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Contact: Varia Sajeniouk 1-416-480-6100 ext 85392 varia.sajeniouk@sunnybrook.ca

Locations
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Canada, Ontario
Odette Cancer Centre, Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Varia Sajeniouk    1-416-480-6100 ext 85392    varia.sajeniouk@sunnybrook.ca   
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Toronto Sunnybrook Regional Cancer Centre
London Regional Cancer Program, Canada
Investigators
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Principal Investigator: Trung N Le Sunnybrook Health Sciences Centre
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Responsible Party: Dr. Trung Le, Trung N. Le MD PhD, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04291209    
Other Study ID Numbers: 1819
First Posted: March 2, 2020    Key Record Dates
Last Update Posted: March 2, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Dr. Trung Le, Sunnybrook Health Sciences Centre:
Hearing Loss
Deafness
Cisplatin-induced Ototoxicity
Sensorineural hearing loss
Ear diseases
Antioxidant
N-acetyl cystein
Additional relevant MeSH terms:
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Hearing Loss
Deafness
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes