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

NCT ID: NCT00716976

Last Updated: 2023-11-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

131 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-23

Study Completion Date

2021-06-30

Brief Summary

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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

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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.

Conditions

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Brain Tumor Central Nervous System Tumor Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor Liver Cancer Neuroblastoma Ototoxicity Ovarian Cancer Sarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

sodium thiosulfate

Intervention Type DRUG

Given IV

examination

Intervention Type PROCEDURE

Patients undergo audiological assessments periodically

Observation Arm (No sodium thiosulfate treatment)

Patients do not receive sodium thiosulfate.

Group Type EXPERIMENTAL

examination

Intervention Type PROCEDURE

Patients undergo audiological assessments periodically

Interventions

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sodium thiosulfate

Given IV

Intervention Type DRUG

examination

Patients undergo audiological assessments periodically

Intervention Type PROCEDURE

Other Intervention Names

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ADH300001 Disodium Thiosulfate Pentahydrate Na Thiosulfate Sodium Hyposulfite Sodium Thiosulphate Thiosulfuric Acid Disodium Salt Pentahydrate Versiclear NSC# 45624 IND#72877

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David R. Freyer, DO, MS

Role: STUDY_CHAIR

Children's Hospital Los Angeles

Locations

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UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

Southern California Permanente Medical Group

Los Angeles, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States

Site Status

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, United States

Site Status

Children's Hospital of New Orleans

New Orleans, Louisiana, United States

Site Status

National Naval Medical Center

Bethesda, Maryland, United States

Site Status

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States

Site Status

Duke Cancer Institute

Durham, North Carolina, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Site Status

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States

Site Status

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States

Site Status

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Children's and Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Site Status

Countries

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United States Australia Canada

References

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Freyer DR, Chen L, Krailo MD, Knight K, Villaluna D, Bliss B, Pollock BH, Ramdas J, Lange B, Van Hoff D, VanSoelen ML, Wiernikowski J, Neuwelt EA, Sung L. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jan;18(1):63-74. doi: 10.1016/S1470-2045(16)30625-8. Epub 2016 Dec 1.

Reference Type DERIVED
PMID: 27914822 (View on PubMed)

Other Identifiers

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COG-ACCL0431

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000588655

Identifier Type: OTHER

Identifier Source: secondary_id

ACCL0431

Identifier Type: -

Identifier Source: org_study_id

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