RATIONALE: Sodium thiosulfate may reduce or prevent hearing loss in young patients receiving cisplatin for cancer. It is not yet known whether sodium thiosulfate is more effective than no additional treatment in preventing hearing loss. PURPOSE: This randomized phase III trial is studying sodium thiosulfate to see how well it works in preventing hearing loss in young patients receiving cisplatin for newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy.
OBJECTIVES: Primary * To compare the efficacy of sodium thiosulfate vs observation in preventing hearing loss in young patients receiving cisplatin for the treatment of newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy. Secondary * To compare the mean change in hearing thresholds for key frequencies in these patients. * To compare the incidences of cisplatin-related grade 3 and 4 nephrotoxicity and grade 3 and 4 cytopenia in these patients. * To compare the event-free survival and overall survival of these patients. * To evaluate the association of two key gene mutations (TPMT and COMT) with the development of cisplatin-induced hearing loss in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to prior cranial radiation (yes vs no), age (\< 5 years vs ≥ 5 years) and duration of cisplatin infusion (\< 2 hours vs ≥ 2 hours). Patients are randomized to 1 of 2 arms. * Arm I (sodium thiosulfate): Patients receive sodium thiosulfate IV over 15 minutes beginning 6 hours after the completion of each cisplatin infusion. Treatment with sodium thiosulfate continues until the completion of cisplatin therapy. * Arm II (observation): Patients do not receive sodium thiosulfate. Patients undergo audiological assessment at baseline, prior to each course of cisplatin, and then at 4 weeks and 1 year after the last course of cisplatin or other cancer treatment. Some patients may undergo saliva collection for DNA studies. After completion of study, patients are followed periodically for 10 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
131
Given IV
Patients undergo audiological assessments periodically
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States
Southern California Permanente Medical Group
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Incidence of Hearing Loss
Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 500 hz
Mean change in hearing threshold (post-pre) at 500 hz.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 1000 hz
Mean change in hearing threshold (post-pre) at 1000 hz.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 2000 hz
Mean change in hearing threshold (post-pre) at 2000 hz
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 4000 hz
Mean change in hearing threshold (post-pre) at 4000 hz.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 8000 hz
Mean change in hearing threshold (post-pre) at 8000 hz.
Time frame: 4 weeks after last dose of cisplatin
Event-Free Survival (EFS)
Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Time frame: 4 years after enrollment
Overall Survival (OS)
Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Time frame: 4 Years after enrollment
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
Time frame: 4 weeks after the last dose of cisplatin
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