A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children
Overview
- Phase
- Phase 3
- Intervention
- sodium thiosulfate
- Conditions
- Brain Tumor
- Sponsor
- Children's Oncology Group
- Enrollment
- 131
- Locations
- 76
- Primary Endpoint
- Incidence of Hearing Loss
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
STS Arm (sodium thiosulfate treatment)
Patients receive sodium thiosulfate IV (dosage 16 g/m2 or 533 mg per kg for patients whose therapeutic protocol administers cisplatin on a per kg basis due to young age or small body) over 15 minutes beginning 6 hours after the completion of each cisplatin infusion. Treatment with sodium thiosulfate continues until the completion of cisplatin therapy.
Intervention: sodium thiosulfate
STS Arm (sodium thiosulfate treatment)
Patients receive sodium thiosulfate IV (dosage 16 g/m2 or 533 mg per kg for patients whose therapeutic protocol administers cisplatin on a per kg basis due to young age or small body) over 15 minutes beginning 6 hours after the completion of each cisplatin infusion. Treatment with sodium thiosulfate continues until the completion of cisplatin therapy.
Intervention: examination
Observation Arm (No sodium thiosulfate treatment)
Patients do not receive sodium thiosulfate.
Intervention: examination
Outcomes
Primary Outcomes
Incidence of Hearing Loss
Time Frame: 4 weeks after last dose of cisplatin
Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
Secondary Outcomes
- Change in Hearing Thresholds For Key Frequencies at 500 hz(4 weeks after last dose of cisplatin)
- Change in Hearing Thresholds For Key Frequencies at 1000 hz(4 weeks after last dose of cisplatin)
- Change in Hearing Thresholds For Key Frequencies at 2000 hz(4 weeks after last dose of cisplatin)
- Change in Hearing Thresholds For Key Frequencies at 4000 hz(4 weeks after last dose of cisplatin)
- Change in Hearing Thresholds For Key Frequencies at 8000 hz(4 weeks after last dose of cisplatin)
- Event-Free Survival (EFS)(4 years after enrollment)
- Overall Survival (OS)(4 Years after enrollment)
- Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)(4 weeks after the last dose of cisplatin)