Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy

Phase 3

Completed

• Conditions: Brain Tumor; Childhood Germ Cell Tumor; Sarcoma; Central Nervous System Tumor; Liver Cancer; Neuroblastoma; Ovarian Cancer; Extragonadal Germ Cell Tumor; Ototoxicity
• Interventions: Drug: sodium thiosulfate; Procedure: examination

• Registration Number: NCT00716976
• Lead Sponsor: Children's Oncology Group

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.

Study Timeline

• Study Start: 2008-06-23
• Study First Submitted: 2008-07-15
• Study First Submitted QC: 2008-07-15
• Study First Posted: 2008-07-16
• Disposition First Submitted: 2014-04-14
• Disposition First Submitted QC: 2014-04-15
• Disposition First Posted: 2014-04-17
• Primary Completion: 2015-04-09
• Results First Submitted: 2016-12-09
• Results First Submitted QC: 2017-05-01
• Results First Posted: 2017-06-01
• Study Completion: 2021-06-30
• Status Verified: 2021-07
• Last Update Submitted: 2023-11-07
• Last Update Posted: 2023-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 131

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
STS Arm (sodium thiosulfate treatment)	sodium thiosulfate	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.
STS Arm (sodium thiosulfate treatment)	examination	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.
Observation Arm (No sodium thiosulfate treatment)	examination	Patients do not receive sodium thiosulfate.

Primary Outcome Measures

Name	Time	Method
Incidence of Hearing Loss	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 Outcome Measures

Name	Time	Method
Change in Hearing Thresholds For Key Frequencies at 500 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 500 hz.
Change in Hearing Thresholds For Key Frequencies at 1000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 1000 hz.
Change in Hearing Thresholds For Key Frequencies at 2000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 2000 hz
Change in Hearing Thresholds For Key Frequencies at 4000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 4000 hz.
Change in Hearing Thresholds For Key Frequencies at 8000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 8000 hz.
Event-Free Survival (EFS)	4 years after enrollment	Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Overall Survival (OS)	4 Years after enrollment	Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)	4 weeks after the last dose of cisplatin

Trial Locations

Locations (76)

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

Rady Children's Hospital - San Diego; 🇺🇸 San Diego, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Connecticut Children's Medical Center; 🇺🇸 Hartford, Connecticut, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Alfred I. duPont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Scroll for more (66 remaining)