Transtympanic STS Against Cisplatin-induced SNHL: the SOUND Trial

NCT ID: NCT07281508

Last Updated: 2025-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-14

Study Completion Date

2030-03-23

Brief Summary

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The goal of this clinical trial is to learn if transtympanic sodium thiosulfate (STS) injections can prevent hearing loss caused by cisplatin chemotherapy in adults with head and neck cancer. The main question it aims to answer is:

Researchers will compare the ear treated with STS gel to the untreated ear within the same patient to see if STS prevents hearing loss.

Participants will:

1. Receive STS gel injections into the middle ear of one ear (randomized) within 3 hours before each cisplatin infusion (3-7 injections per patient).
2. Undergo hearing tests at baseline and 2-4 months after the last cisplatin treatment.
3. Complete questionnaires about hearing and tinnitus at baseline and 2-4 months after treatment.

Detailed Description

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Trial design:

This study is an investigator-initiated randomized controlled multicenter phase III trial. Patient accrual and treatment (treatment and hearing analysis will take 22 weeks per patient) will start in 2025 and will be completed in 2028. Afterwards, the patients will have a routine follow-up for a median of 2 years to collect necessary survival data (2025-2030).

Trial population:

A hundred patients with solid head and neck malignancies who are treated with ≥ 200 mg/m2 cisplatin will be included. To be eligible for participation, patients must be 18 years or older. Study participation is not possible if more than 30 gray radiotherapy is applied to the inner ear, asymmetric hearing loss or more than 40 dB hearing loss is detected before start of treatment, known hypersensitivity to STS injections, and/or if patients have ear conditions that prevent middle ear injections from being administered properly.

Interventions:

Patients will be treated with an STS injection in one ear and no treatment in the contralateral ear. The ear to be treated with STS gel will be determined by randomization. The hearing of the treated ear will then be compared with the untreated ear. The audiometrist who conducts the hearing test will not know which ear has been treated with sodium thiosulfate. Hence, the design of this trial takes advantage of the fact that every patient has two ears, and offers the unique concept of having a randomized controlled comparison of platinum-induced hearing loss of the treated versus the untreated ear within individual patients. This results in the advantage that during the analysis of the results differences between patients are eliminated. The STS gel will be injected into the middle ear within three hours before each cisplatin infusion (range 3-7 injections per patient) into one ear, the other ear will be left untreated. Hearing tests will be conducted at baseline (before the first cisplatin therapy) and 3 months (range 2 - 4) after the last cisplatin infusion. Questionnaires will be filled in to document hearing-related complaints at baseline and 3 months (range 2 - 4) after the last cisplatin treatment. For the survival analysis on a median of 1 and 2 years after treatment, survival data will be collected from the patient's medical records. These data will be compared to similar patients from historical data. In a pilot of 10 patients in the LUMC vestibular testing will be performed at baseline and 6 weeks after the last cisplatin infusion.

Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks:

Based on the results of our successfully completed phase I study, we expect that 30-50% of patients will experience a noticeable difference between the STS-treated and untreated ear (2). The STS injections in the middle ear carry small risk. Our phase 1 study has shown that administrations of sodium thiosulfate are safe. The possible risks/side effects of the injections are pain, temporary fullness in the ear, temporary dizziness, and temporary decreased hearing. There is also a very small (\<1%) risk of permanent perforation of the eardrum. The injections will be given before every cisplatin treatment because sodium thiosulfate remains available in the middle and inner ear for only a temporary period. The METC does not agree with the use of a placebo control, as the risk of a complication (albeit small) is not acceptable. The current standard of care is 'no treatment' and the audiogram provides a sufficiently objective measurement. Therefore, the study design is changed to a non-placebo randomised controlled trial and only the audiometrist is blinded.

Conditions

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Cisplatin-related Hearing Loss

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Transtympanic sodium thiosulphate (STS) 0.1M/0,5% hyaluronate

One ear of a patient: The transtympanic sodium thiosulphate is administered into one ear of a patient. The intervention takes place within 3 hours before each cisplatin course. The intervention takes place 3 to 7 times, depending on the cisplatin schedule

Group Type EXPERIMENTAL

Transtympanic sodium thiosulphate (STS) 0.1M/0,5% hyaluronate

Intervention Type DRUG

The transtympanic injection gel is composed of the following components:

* Sodium Thiosulfate 250mg/mL, 10mL for injection (STS)
* BiolevoxTM HA 2,2%, 2mL, pre-filled syringe for intraarticular injection (HYA)
* Sterile Phosphate-buffered Sodium Chloride, 500mL (PBS)

Untreated ear

The other ear of the same patient is left untreated

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Transtympanic sodium thiosulphate (STS) 0.1M/0,5% hyaluronate

The transtympanic injection gel is composed of the following components:

* Sodium Thiosulfate 250mg/mL, 10mL for injection (STS)
* BiolevoxTM HA 2,2%, 2mL, pre-filled syringe for intraarticular injection (HYA)
* Sterile Phosphate-buffered Sodium Chloride, 500mL (PBS)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Histological or cytological proof of solid head and neck malignancies with an indication for treatment with cisplatin in a cumulative dose of ≥ 200mg/m2 given in a weekly schedule of 7 times 40 mg/m2 or a 3-weekly schedule of 3 times 100 mg/m2
* Treatment with high-dose cisplatin (cumulative dose ≥ 200mg/m2) of maximum 7 cycles
* Able and willing to give written informed consent;
* WHO performance status of 0, 1 or 2;
* Age older than 18 years.

Exclusion Criteria

* Asymmetric hearing capacity (SNHL) prior to treatment, defined as a difference between both ears in hearing capacity of ≥ 10 dB averaged over 3 adjacent frequencies in the range of 0.5 to 12.5 kHz (i.e. 0.5, 1, 2, 4, 8, 10 and 12.5 kHz).
* Baseline hearing: more than 40 dB SNHL at PTA 1-2-4 kHz (in one or both ears)
* A planned radiation dose of \> 30 Gy to the cochlea (8);
* Known hypersensitivity to STS-containing HYA gel formulation;
* Any condition that would, according to the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures;
* Otologic pathology that hampers the transtympanically applied STS gel to diffuse through the round window, e.g. otosclerosis, a narrow ear canal, otitis media with effusion.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Netherlands Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lotje Zuur, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

AVL

Locations

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Antoni van Leeuwenhoek

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status RECRUITING

Erasmus Universitair Medisch Centrum Rotterdam

Rotterdam, South Holland, Netherlands

Site Status NOT_YET_RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Site Status NOT_YET_RECRUITING

Stichting Radboud University Medical Center

Nijmegen, , Netherlands

Site Status NOT_YET_RECRUITING

Countries

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Netherlands

Central Contacts

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Daniël Griffioen, MD

Role: CONTACT

+31205129111

Jeany Rademaker-Lakhai, PhD

Role: CONTACT

0205129111

Facility Contacts

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Daniël Griffioen, MD

Role: primary

+31205129111

Jeany Rademaker-Lakhai, PhD

Role: backup

+31205129111

Jeroen Jansen, Prof.

Role: primary

+31715269111

Stijn Keereweer, Dr.

Role: primary

+31107040704

Robert Stokroos, Prof.

Role: primary

+31887555555

Froukje Cals, Dr.

Role: primary

+31243611111

Other Identifiers

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M21STS

Identifier Type: -

Identifier Source: org_study_id

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