Pediatric blood & cancer · 2025
Feasibility and Safety of Intratympanic Administration of Sustained-Exposure Dexamethasone Thermosensitive Gel (OTO-104) for Prevention of Cisplatin-Induced Hearing Loss in Children: A Multisite Phase 2 Randomized Clinical Trial.
СтатьяКлиническое исследование II фазыРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Freyer David R, Ohlsen Timothy J D, Don Debra, Orgel Etan, Hayashi Robert J, Lieu Judith E, Foster Jennifer H, Sitton Matthew S, Geller James I, Choo Daniel I, Rangaswami Arun, Chang Kay W, Greffe Brian, Chan Kenny, Lee Alice, Grunstein Eli, O'Neill Allison F, Rahbar Reza, Anderson Jeffery J
Аннотация
BACKGROUND: Cisplatin-induced hearing loss (CIHL) remains a significant complication of pediatric cancer treatment. We evaluated the feasibility, safety, and trends of the efficacy of intratympanic injections of sustained-exposure dexamethasone thermosensitive gel (OTO-104) for otoprotection.
PROCEDURE: In this multisite randomized phase 2 trial (NCT02997189), patients aged 0.5-21 years with newly diagnosed cancer treated with cisplatin were eligible. Participants' ears were randomized to receive up to three intratympanic injections of 0.2 mL OTO-104 in one ear and no treatment contralaterally. OTO-104 was administered by an otolaryngologist within 72 hours preceding each cisplatin cycle. Feasibility was determined by the successful administration of intended doses. Treatment-emergent adverse events (TEAEs) and outcomes were monitored by physical examination, concurrent medications, otoscopy, tympanometry, and audiometry.
RESULTS: From January 6 to September 26, 2017, 18 doses of OTO-104 were administered to 11 evaluable participants across 5 centers (range, 1-14 years; 9 neuroblastoma and 2 osteosarcoma) via intratympanic injection (9) or tympanostomy tube (2). Sixteen injections were paired with other procedural sedations and two were performed awake; all injections were successfully delivered. The median interval between OTO-104 and cisplatin was 14 hours (range, 7-64). Clinically insignificant tympanic scabs were noted in five participants; no middle ear changes were observed. There were three otologic TEAEs (two transient mild-moderate otalgia [related] and one hypoacusis [unrelated]) and no related non-otologic TEAEs. CIHL developed similarly in treated versus untreated ears; the trial was terminated early.
CONCLUSIONS: Although dexamethasone at this dose was not otoprotective, these results suggest that intratympanic injection may be safe, feasible, and a viable delivery platform for testing other otoprotectants.
PROCEDURE: In this multisite randomized phase 2 trial (NCT02997189), patients aged 0.5-21 years with newly diagnosed cancer treated with cisplatin were eligible. Participants' ears were randomized to receive up to three intratympanic injections of 0.2 mL OTO-104 in one ear and no treatment contralaterally. OTO-104 was administered by an otolaryngologist within 72 hours preceding each cisplatin cycle. Feasibility was determined by the successful administration of intended doses. Treatment-emergent adverse events (TEAEs) and outcomes were monitored by physical examination, concurrent medications, otoscopy, tympanometry, and audiometry.
RESULTS: From January 6 to September 26, 2017, 18 doses of OTO-104 were administered to 11 evaluable participants across 5 centers (range, 1-14 years; 9 neuroblastoma and 2 osteosarcoma) via intratympanic injection (9) or tympanostomy tube (2). Sixteen injections were paired with other procedural sedations and two were performed awake; all injections were successfully delivered. The median interval between OTO-104 and cisplatin was 14 hours (range, 7-64). Clinically insignificant tympanic scabs were noted in five participants; no middle ear changes were observed. There were three otologic TEAEs (two transient mild-moderate otalgia [related] and one hypoacusis [unrelated]) and no related non-otologic TEAEs. CIHL developed similarly in treated versus untreated ears; the trial was terminated early.
CONCLUSIONS: Although dexamethasone at this dose was not otoprotective, these results suggest that intratympanic injection may be safe, feasible, and a viable delivery platform for testing other otoprotectants.