Randomized phase 1 trial of cisplatin-based chemotherapy with or without sodium thiosulfate for men with metastatic germ cell tumor (GCT).

Abstract

TPS5131 Background: Cisplatin-induced ototoxicity remains a major survivorship issue in men with metastatic GCT. Sanchez et al., demonstrated that among adult GCT survivors, 78% develop hearing loss, with severity associated with cumulative cisplatin exposure. Sodium thiosulfate (STS; PEDMARK) was FDA-approved in 2022 to reduce the risk of cisplatin-associated ototoxicity in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. However, prospective data in adults with metastatic GCT receiving curative intent cisplatin-based therapy are lacking. This study aims to address this gap in men with metastatic GCT, and potentially improve long-term quality of life. Methods: This open-label, single-center, randomized phase 1 trial evaluates sodium thiosulfate for reducing the incidence of cisplatin-induced ototoxicity in adults with metastatic GCT. Eligible adults have stage II–III GCT and are planned for first- or second-line cisplatin-based chemotherapy; patients receiving second-line therapy require a ≥4-week cisplatin washout to establish a new audiometric baseline. Key exclusions include baseline moderate or greater hearing loss, hypersensitivity to sodium thiosulfate or related compounds, chronic systemic corticosteroid use, concurrent non-cisplatin ototoxic medications, and comorbidities requiring sodium restrictions. Participants are randomized 2:1 to receive cisplatin-based chemotherapy with sodium thiosulfate versus chemotherapy alone, with a target enrollment of 39 patients. Sodium thiosulfate is administered intravenously at 20 g/m² over 30 minutes, beginning 6 hours after completion of cisplatin infusion and at least 10 hours before the next cisplatin dose, consistent with FDA-approved multi-day dosing schedules. The primary endpoint is the incidence of clinically meaningful ototoxicity, defined by trial parameters using American Speech-Language-Hearing Association criteria relative to baseline audiometry. Secondary endpoints include incidence of high-frequency ototoxicity, ototoxicity severity, safety per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and 2-year progression-free survival. Ototoxicity monitoring is performed using serial high-frequency audiometry (testing 250–12,500 Hz) at baseline and 1, 3, and 6 months following completion of cisplatin therapy. Ototoxicity incidence will be compared between arms using a one-sided Fisher’s exact test under a modified intention-to-treat framework. Enrollment has begun. Clinical trial information: NCT07218913 .