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

Ovarian Cancer Clinical Trial

Official title:

A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00716976
• Other study ID #: ACCL0431
• Secondary ID: COG-ACCL0431CDR0
• Status: Completed
• Phase: Phase 3
• Start date: June 23, 2008
• Est. completion date: June 30, 2021

Study information

• Verified date: July 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: June 30, 2021
• Est. primary completion date: April 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

DISEASE CHARACTERISTICS:

• Newly diagnosed (previously untreated or currently receiving cancer treatment for the diagnosis that made the patient eligible for this study) with germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy

• Planning to receive a chemotherapy treatment regimen that includes a cumulative cisplatin dose = 200 mg/m² with individual cisplatin doses to be infused over = 6 hours

• Enrolled on hearing assessment clinical trial COG-ACCL05C1

• Normal auditory results

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (for patients > 16 years of age)

• Lansky PS 50-100% (for patients = 16 years of age)

• Serum sodium normal

• Absolute granulocyte count > 1,000/mm³

• Platelet count > 100,000/mm³

• Creatinine clearance or radioisotope glomerular filtration rate = 70mL/min OR serum creatinine between 0.4 and 1.7 mg/dL, based on age and gender

• Total bilirubin = 1.5 times upper limit of normal (ULN) for age

• AST or ALT < 2.5 times ULN for age

• Not pregnant or nursing

• Negative pregnancy test (if patient has child-bearing capacity)

• Fertile patients must use effective contraception

• No known hypersensitivity to sodium thiosulfate or other thiol agents (e.g., amifostine trihydrate, N-acetylcysteine, MESNA, or captopril)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior platinum-based chemotherapy (cisplatin or carboplatin)

• Other prior chemotherapy allowed

• Prior cranial radiotherapy (e.g., for treatment of medulloblastoma) allowed provided normal hearing is documented after completion of radiotherapy and before enrollment and administration of cisplatin chemotherapy

• At least 6 months since prior hematopoietic stem cell transplantation.

• No evidence of graft-versus-host disease

• No concurrent enrollment on another COG clinical trial for treatment of the cancer.

• Concurrent enrollment on a non-COG clinical trial (e.g., Head start) allowed.

• Cranial irradiation after the completion of all systemic chemotherapy allowed provided post end-of-treatment audiometry is completed prior to beginning irradiation.

• Concurrent radiotherapy to extracranial sites allowed.

Related Conditions & MeSH terms

• Brain Tumor
• Central Nervous System Neoplasms
• Central Nervous System Tumor
• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Hepatoblastoma
• Liver Cancer
• Liver Neoplasms
• Medulloblastoma
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Neuroblastoma
• Osteosarcoma
• Ototoxicity
• Ovarian Cancer
• Sarcoma

Intervention

Drug:
• sodium thiosulfate
Given IV

Procedure:
• examination
Patients undergo audiological assessments periodically

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Hearing Loss	Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.	4 weeks after last dose of cisplatin
Secondary	Change in Hearing Thresholds For Key Frequencies at 500 hz	Mean change in hearing threshold (post-pre) at 500 hz.	4 weeks after last dose of cisplatin
Secondary	Change in Hearing Thresholds For Key Frequencies at 1000 hz	Mean change in hearing threshold (post-pre) at 1000 hz.	4 weeks after last dose of cisplatin
Secondary	Change in Hearing Thresholds For Key Frequencies at 2000 hz	Mean change in hearing threshold (post-pre) at 2000 hz	4 weeks after last dose of cisplatin
Secondary	Change in Hearing Thresholds For Key Frequencies at 4000 hz	Mean change in hearing threshold (post-pre) at 4000 hz.	4 weeks after last dose of cisplatin
Secondary	Change in Hearing Thresholds For Key Frequencies at 8000 hz	Mean change in hearing threshold (post-pre) at 8000 hz.	4 weeks after last dose of cisplatin
Secondary	Event-Free Survival (EFS)	Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.	4 years after enrollment
Secondary	Overall Survival (OS)	Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.	4 Years after enrollment
Secondary	Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)		4 weeks after the last dose of cisplatin