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.

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): University of Illinois Cancer Center
🇺🇸
Chicago, Illinois, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸
Miami, Florida, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸
Las Vegas, Nevada, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸
Dallas, Texas, United States
Riley's Children Cancer Center at Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Geisinger Cancer Institute at Geisinger Health
🇺🇸
Danville, Pennsylvania, United States
Childrens Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Southern California Permanente Medical Group
🇺🇸
Los Angeles, California, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Nemours Children's Clinic - Pensacola
🇺🇸
Pensacola, Florida, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Cardinal Glennon Children's Hospital
🇺🇸
Saint Louis, Missouri, United States
East Tennessee Children's Hospital
🇺🇸
Knoxville, Tennessee, United States
Mountain States Tumor Institute at St. Luke's Regional Medical Center
🇺🇸
Boise, Idaho, United States
Hackensack University Medical Center Cancer Center
🇺🇸
Hackensack, New Jersey, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸
Iowa City, Iowa, United States
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
SUNY Upstate Medical University Hospital
🇺🇸
Syracuse, New York, United States
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Rainbow Babies and Children's Hospital
🇺🇸
Cleveland, Ohio, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸
Providence, Rhode Island, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸
Bethlehem, Pennsylvania, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸
New York, New York, United States
Children's Hospital of The King's Daughters
🇺🇸
Norfolk, Virginia, United States
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Hopital Sainte Justine
🇨🇦
Montreal, Quebec, Canada
Masonic Cancer Center at University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Duke Cancer Institute
🇺🇸
Durham, North Carolina, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸
San Francisco, California, United States
Children's and Women's Hospital of British Columbia
🇨🇦
Vancouver, British Columbia, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦
Saskatoon, Saskatchewan, Canada
Nemours Children's Clinic
🇺🇸
Jacksonville, Florida, United States
Oklahoma University Cancer Institute
🇺🇸
Oklahoma City, Oklahoma, United States
UAB Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
Legacy Emanuel Children's Hospital
🇺🇸
Portland, Oregon, United States
Knight Cancer Institute at Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦
Quebec, Canada
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸
Tampa, Florida, United States
National Naval Medical Center
🇺🇸
Bethesda, Maryland, United States
Mayo Clinic Cancer Center
🇺🇸
Rochester, Minnesota, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Alfred I. duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸
Alexandria, Louisiana, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸
Charlotte, North Carolina, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸
Sioux Falls, South Dakota, United States
Marshfield Clinic - Marshfield Center
🇺🇸
Marshfield, Wisconsin, United States
Providence Cancer Center at Sacred Heart Medical Center
🇺🇸
Spokane, Washington, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸
Green Bay, Wisconsin, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Yale Cancer Center
🇺🇸
New Haven, Connecticut, United States
Nemours Children's Clinic - Orlando
🇺🇸
Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸
Winston-Salem, North Carolina, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
🇺🇸
Ann Arbor, Michigan, United States
Children's Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
Cancer Research Center of Hawaii
🇺🇸
Honolulu, Hawaii, United States
Children's Hospital of New Orleans
🇺🇸
New Orleans, Louisiana, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸
Richmond, Virginia, United States