Transtympanic STS Against Cisplatin-induced SNHL: the SOUND Trial
ConditionCisplatin-related Hearing Loss
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Netherlands Cancer Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Parallel
Treatments tested in this trial
Transtympanic sodium thiosulphate (STS) 0.1M/0,5% hyaluronate
DrugThe 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)
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: Transtympanic sodium thiosulphate (STS) 0.1M/0,5% hyaluronateExperimental treatment 1 intervention
Group B: Untreated earNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
The efficacy (clinically relevant benefit) of transtympanic STS 0.1M/0.5 HYA against platinum-related ototoxicity.
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.
Time frame
Baseline and 2-4 months after last cycle of chemotherapySecondary outcomes
1
The superiority of STS versus untreated ear with regard to hearing capacity based on audiometry.
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.
Time frame
Baseline and 2-4 months after last cycle of chemotherapy2
The superiority of STS versus untreated ear with regard to hearing loss based on American Speech-Language-Hearing Association criteria (ASHA).
The difference in sensorineural hearing loss between STS- and placebo-treated ears based on the ASHA criteria: * 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 (this refers specifically to the highest frequencies tested, where earlier responses are obtained close to the limits of the audiometric output and later responses cannot be obtained at the limits of the audiometer).
Time frame
Baseline and 2-4 months after last cycle of chemotherapy3
The superiority of STS versus untreated ear with regard to hearing loss based on TUNE criteria.
The difference in sensorineural hearing loss between STS- and placebo-treated ears based on the TUNE criteria: * 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 kHz de novo
Time frame
Baseline and 2-4 months after last cycle of chemotherapy4
The superiority of STS versus placebo-treated ear with regard to hearing loss based on the Common Terminology Criteria for Adverse Eventes (CTCAE) criteria.
The difference in sensorineural hearing loss between the STS- and placebo treated ears based on the CTCAE criteria (40): * Grade 1: threshold shift of 15 - 25 dB averaged at 2 contiguous test frequencies in at least one ear OR subjective change in hearing in the absence of documented hearing loss; * Grade 2: threshold shift of \> 25 dB averaged at 2 contiguous test frequencies in at least one ear; * Grade 3: threshold shift of \> 25 dB averaged at 3 contiguous test frequencies in at least one ear OR hearing aid or intervention indicated * Grade 4: Decrease in hearing to profound bilateral loss (absolute threshold \> 80 dB HL at 2 kHz and above); non-serviceable hearing
Time frame
Baseline and 2-4 months after last cycle of chemotherapy.Other outcomes
1
Cisplatin-related vestibulotoxicity
To assess cisplatin related vestibulotoxicity based on vestibular testing (V-HIT) at baseline and 6 weeks post-treatment in the STS-treated ear versus untreated ear and to evaluate the preventive effect of transtympanic STS injections on cisplatin-related vestibulotoxicity.
Time frame
Baseline and 6 weeks after last cycle of chemotherapy.Sponsors and contacts
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Source ClinicalTrials.gov