Transtympanic sodium thiosulfate to prevent cisplatin-related hearing loss, a randomized controlled multicenter phase III trial; The SOUND trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Het Nederlands Kanker Instituut-Antoni Van Leeuwenhoek Ziekenhuis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09], Diseases [C] - Neoplasms [C04]

Trial duration

14 Apr 2025 → ongoing

Decision date (initial)

2023-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy

To assess the efficacy (i.e. clinically relevant benefit) of transtympanic STS 0.1M/0.5 HYA against platinum-related ototoxicity.

Secondary objectives 6

1. The superiority of STS versus untreated ear with regard to hearing capacity based on audiometry;
2. The superiority of STS versus untreated ear with regard to hearing loss based on American Speech-Language-Hearing Association criteria (ASHA)(38)
3. The superiority of STS versus untreated ear with regard to hearing loss based on TUNE criteria (39)
4. The superiority of STS versus untreated ear with regard to hearing loss based on the Common Terminology Criteria for Adverse Eventes (CTCAE) criteria (40)
5. The median 1- and 2-year Survival
6. Quality of life/Patient-related outcome measures (PROM). Subjective hearing loss after platinum treatment.

Conditions and MedDRA coding

Head and Neck squamous cell carcinoma

Regulatory references

Plan to share IPD

Yes

IPD plan description

‘For future research, other than defined in the protocol, a request for use of the data has to be performed. Only with ethical clearance by the METC or IRB NKI, an investigator will be allowed to use this data’.”

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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
2. Treatment with high-dose cisplatin (cumulative dose ≥ 200mg/m2) of maximum 7 cycles
3. Able and willing to give written informed consent
4. WHO performance status of 0, 1 or 2
5. Age older than 18 years

Exclusion criteria 6

1. Asymmetric hearing capacity (SNHL) prior to treatment, defined as an difference between both ears in hearing capacity of ≥ 10 dB averaged over 3 adjacent frequencies, ≥ 15 dB averaged over 2 adjacent frequencies and ≥ 20 dB at any one frequency in the range of 500-14 kHz, according to the NOAH-4 criteria (43)
2. Baseline hearing: more than 40 dB sensorineural hearing loss at PTA 1-2-4 kHz (in one or both ears)
3. A planned radiation dose of > 30 Gy to the cochlea (4)
4. Known hypersensitivity to STS-containing HYA gel formulation
5. 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
6. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percent of patients with a clinically relevant benefit of transtympanic STS injection against CIHL, defined as the change in the threshold between baseline and 3 months after treatment differs by ≥ 10 dB at any three adjacent frequencies from 0.5 to 16 kHz in favour of the STS treated ear.

Secondary endpoints 6

1. Mean difference between STS- and untreated ears in threshold shift (post-treatment minus baseline hearing, in a continuous scale) at sensorineural pure tone averages (PTA) 1-2-4 kHz and 8-10-12.5 kHz in dB.
2. The difference in sensorineural hearing loss between STS- and untreated ears based on the ASHA criteria(38): Grade A: threshold shift ≥ 20 dB at any one test frequency; Grade B: threshold shift ≥ 10 dB at 2 consecutive frequencies; Grade C: loss of response at three consecutive test frequencies where responses were previously obtained
3. The difference in sensorineural hearing loss between STS- and untreated ears based on the TUNE criteria (39) Grade 0: No hearing loss Grade 1a: threshold shift >10dB at PTA 8-10-12.5 kHz OR subjective hearing changes without threshold shift Grade 1b: threshold shift >10dB at PTA 1-2-4 kHz Grade 2a: threshold shift >20dB at PTA 8-10-12.5 kHz Grade 2b: threshold shift >20dB at PTA 1-2-4 kHz Grade 3: Hearing level >35dB HL at PTA 1-2-4 kHz de novo Grade 4: Hearing level >70dB HL at PTA 1-2-4
4. The difference in sensorineural hearing loss between the STS- and untreated ears based on the CTCAE criteria (40)
5. Disease-specific survival, recurrence-free and overall survival measured at median 1 and 2 years after the start of treatment.
6. 6. Quality of life/Patient-related outcome measures (PROM). Subjective hearing loss after platinum treatment. Measured by two questionnaires: a) Speech, Spatial and Qualities of Hearing scale (SSQ) compare; b) Tinnitus Handicap Inventory (THI)-12.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Het Nederlands Kanker Instituut-Antoni Van Leeuwenhoek Ziekenhuis

Sponsor organisation

Stichting Het Nederlands Kanker Instituut-Antoni Van Leeuwenhoek Ziekenhuis

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Stichting Het Nederlands Kanker Instituut-Antoni Van Leeuwenhoek Ziekenhuis

Contact name

Anouk Burger

Public contact point

Organisation

Stichting Het Nederlands Kanker Instituut-Antoni Van Leeuwenhoek Ziekenhuis

Contact name

Anouk Burger

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications