Transtympanic sodium thiosulfate to prevent cisplatin-related hearing loss

Transtympanic Sodium Thiosulfate to Prevent Cisplatin-related Hearing Loss A Randomized Controlled Multicenter Phase III Trial; The SOUND Trial

This trial will test whether injecting sodium thiosulfate gel into one middle ear can prevent hearing loss from cisplatin chemotherapy in adults with head and neck cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Drugs / interventions: radiation, chemotherapy
• Locations: 5 sites (Amsterdam, North Holland and 4 other locations)
• Trial ID: NCT07281508 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized phase III trial that uses each patient as their own control by treating one ear with transtympanic sodium thiosulfate (STS) gel and leaving the other ear untreated. About 100 adults with head and neck cancers who will receive a cumulative cisplatin dose ≥200 mg/m2 will be randomized to receive the STS injection into one ear within three hours before each cisplatin infusion (3–7 injections per patient). Hearing tests and questionnaires are done at baseline and 2–4 months after the last cisplatin dose, and the audiometrist conducting tests is blinded to which ear was treated. Patients will have routine follow-up for survival data for a median of about two years after treatment.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed solid head and neck malignancies scheduled to receive high-dose cisplatin (cumulative ≥200 mg/m2), with baseline symmetric hearing better than 40 dB PTA and no conditions preventing middle ear injection.

Not a fit: Patients with significant baseline asymmetric or >40 dB hearing loss, planned cochlear radiation >30 Gy, known hypersensitivity to the STS gel, or ear anatomy/conditions that preclude transtympanic injections are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could preserve hearing in the treated ear and reduce the overall burden of cisplatin-related hearing loss for patients receiving high-dose cisplatin.

How similar studies have performed: Systemic sodium thiosulfate has reduced cisplatin ototoxicity in some pediatric studies, and smaller early-phase studies of local transtympanic STS have suggested protective potential, but this within-patient phase III design is novel.

Eligibility criteria

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.

Where this trial is running

Amsterdam, North Holland and 4 other locations

• Antoni van Leeuwenhoek — Amsterdam, North Holland, Netherlands (Recruiting)
• Leiden University Medical Center — Leiden, South Holland, Netherlands (Recruiting)
• Erasmus Universitair Medisch Centrum Rotterdam — Rotterdam, South Holland, Netherlands (Not_yet_recruiting)
• University Medical Center Utrecht — Utrecht, Utrecht, Netherlands (Not_yet_recruiting)
• Stichting Radboud University Medical Center — Nijmegen, Netherlands (Not_yet_recruiting)

Study contacts

• Principal investigator: Lotje Zuur, Prof. Dr. — Avl
• Study coordinator: Daniël Griffioen, MD

Conditions Cisplatin-related Hearing Loss