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

November 7, 2023 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

131

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
  • Canada
      • Quebec, Canada, G1V 4G2
        • Centre Hospitalier Universitaire de Quebec
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • Children's and Women's Hospital of British Columbia
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3J 3G9
        • IWK Health Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre at the University of Saskatchewan
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • UAB Comprehensive Cancer Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • California
      • Los Angeles, California, United States, 90027
        • Southern California Permanente Medical Group
      • Los Angeles, California, United States, 90027
        • Childrens Hospital Los Angeles
      • Madera, California, United States, 93638-8762
        • Children's Hospital Central California
      • San Diego, California, United States, 92123-4282
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
      • New Haven, Connecticut, United States, 06520-8028
        • Yale Cancer Center
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I. DuPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Lee Cancer Care of Lee Memorial Health System
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center - Miami
      • Orlando, Florida, United States, 32803-1273
        • Florida Hospital Cancer Institute at Florida Hospital Orlando
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic - Orlando
      • Pensacola, Florida, United States, 32504
        • Nemours Children's Clinic - Pensacola
      • Saint Petersburg, Florida, United States, 33701
        • All Children's Hospital
      • Tampa, Florida, United States, 33607
        • St. Joseph's Cancer Institute at St. Joseph's Hospital
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Cancer Research Center of Hawaii
    • Idaho
      • Boise, Idaho, United States, 83712-6297
        • Mountain States Tumor Institute at St. Luke's Regional Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612-7243
        • University of Illinois Cancer Center
      • Peoria, Illinois, United States, 61603
        • Saint Jude Midwest Affiliate
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley's Children Cancer Center at Riley Hospital for Children
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Blank Children's Hospital
      • Iowa City, Iowa, United States, 52242-1002
        • Holden Comprehensive Cancer Center at University of Iowa
    • Kentucky
      • Louisville, Kentucky, United States, 40232
        • Kosair Children's Hospital
    • Louisiana
      • Alexandria, Louisiana, United States, 71315-3198
        • Tulane Cancer Center Office of Clinical Research
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital of New Orleans
    • Maryland
      • Bethesda, Maryland, United States, 20889-5600
        • National Naval Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0286
        • C.S. Mott Children's Hospital at University of Michigan Medical Center
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Kalamazoo, Michigan, United States, 49007-5381
        • Bronson Methodist Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • Nevada
      • Las Vegas, Nevada, United States, 89109-2306
        • CCOP - Nevada Cancer Research Foundation
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Cancer Center
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131-5636
        • University of New Mexico Cancer Center
    • New York
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28233-3549
        • Presbyterian Cancer Center at Presbyterian Hospital
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Institute
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44106-5000
        • Rainbow Babies and Children's Hospital
      • Columbus, Ohio, United States, 43205-2696
        • Nationwide Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Cancer Institute
    • Oregon
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Children's Hospital
      • Portland, Oregon, United States, 97239-3098
        • Knight Cancer Institute at Oregon Health and Science University
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Lehigh Valley Hospital - Muhlenberg
      • Danville, Pennsylvania, United States, 17822-0001
        • Geisinger Cancer Institute at Geisinger Health
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh of UPMC
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital Comprehensive Cancer Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5039
        • Sanford Cancer Center at Sanford USD Medical Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Children's Hospital
    • Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
      • San Antonio, Texas, United States, 78207
        • University of Texas Health Science Center at San Antonio
    • Virginia
      • Norfolk, Virginia, United States, 23507-1971
        • Children's Hospital of The King's Daughters
      • Richmond, Virginia, United States, 23298-0037
        • Virginia Commonwealth University Massey Cancer Center
    • Washington
      • Spokane, Washington, United States, 99220-2555
        • Providence Cancer Center at Sacred Heart Medical Center
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54307-3508
        • St. Vincent Hospital Regional Cancer Center
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic - Marshfield Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: sodium thiosulfate
Given IV
Other Names:
  • Sodium Thiosulphate
  • ADH300001
  • Disodium Thiosulfate Pentahydrate
  • Na Thiosulfate
  • Sodium Hyposulfite
  • Thiosulfuric Acid
  • Disodium Salt
  • Pentahydrate
  • Versiclear
  • NSC# 45624
  • IND#72877
Procedure: examination
Patients undergo audiological assessments periodically
Experimental: Observation Arm (No sodium thiosulfate treatment)
Patients do not receive sodium thiosulfate.
Procedure: examination
Patients undergo audiological assessments periodically

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 weeks after last dose of cisplatin

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: David R. Freyer, DO, MS, Children's Hospital Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 23, 2008

Primary Completion (Actual)

April 9, 2015

Study Completion (Actual)

June 30, 2021

Study Registration Dates

First Submitted

July 15, 2008

First Submitted That Met QC Criteria

July 15, 2008

First Posted (Estimated)

July 16, 2008

Study Record Updates

Last Update Posted (Actual)

November 9, 2023

Last Update Submitted That Met QC Criteria

November 7, 2023

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACCL0431
  • COG-ACCL0431 (Other Identifier: Children's Oncology Group)
  • CDR0000588655 (Other Identifier: Clinical Trials.gov)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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