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

Phase 3
1 Year
18 Years
Open (Enrolling)
Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor, Liver Cancer, Neuroblastoma, Ototoxicity, Ovarian Cancer, Sarcoma

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Trial Information

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



- 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


- 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.

Inclusion Criteria


- 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

- Enrolled on hearing assessment clinical trial COG-ACCL05C1

- Normal auditory results


- 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)


- 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., Headstart) allowed

- No concurrent cranial irradiation during the chemotherapy regimen (i.e., prior to the
administration of the final dose of cisplatin)

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

- Concurrent radiotherapy to extracranial sites allowed

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Incidence of hearing loss

Safety Issue:


Principal Investigator

David R. Freyer, DO, MS

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Los Angeles



Study ID:




Start Date:

June 2008

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Childhood Germ Cell Tumor
  • Extragonadal Germ Cell Tumor
  • Liver Cancer
  • Neuroblastoma
  • Ototoxicity
  • Ovarian Cancer
  • Sarcoma
  • ototoxicity
  • childhood central nervous system germ cell tumor
  • childhood extracranial germ cell tumor
  • childhood extragonadal germ cell tumor
  • childhood malignant testicular germ cell tumor
  • childhood malignant ovarian germ cell tumor
  • childhood teratoma
  • childhood medulloblastoma
  • disseminated neuroblastoma
  • regional neuroblastoma
  • localized resectable neuroblastoma
  • localized unresectable neuroblastoma
  • stage 4S neuroblastoma
  • localized osteosarcoma
  • metastatic osteosarcoma
  • childhood hepatoblastoma
  • stage I childhood liver cancer
  • stage II childhood liver cancer
  • stage III childhood liver cancer
  • stage IV childhood liver cancer
  • Liver Neoplasms
  • Medulloblastoma
  • Nervous System Neoplasms
  • Neuroblastoma
  • Osteosarcoma
  • Ovarian Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Hepatoblastoma
  • Sarcoma



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Mayo Clinic Cancer Center Rochester, Minnesota  55905
Hurley Medical Center Flint, Michigan  48503
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
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Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Marshfield Clinic - Marshfield Center Marshfield, Wisconsin  54449
Newark Beth Israel Medical Center Newark, New Jersey  07112
Holden Comprehensive Cancer Center at University of Iowa Iowa City, Iowa  52242-1002
Cancer Research Center of Hawaii Honolulu, Hawaii  96813
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Mercy Hospital Kansas City, Missouri  64108
Nemours Children's Clinic Jacksonville, Florida  32207
All Children's Hospital St. Petersburg, Florida  33701
Saint Jude Midwest Affiliate Peoria, Illinois  61637
Children's Hospital of New Orleans New Orleans, Louisiana  70118
Cardinal Glennon Children's Hospital Saint Louis, Missouri  63104
Driscoll Children's Hospital Corpus Christi, Texas  78466
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
East Tennessee Children's Hospital Knoxville, Tennessee  37901
Children's Hospital of the King's Daughters Norfolk, Virginia  23507
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Yale Cancer Center New Haven, Connecticut  06520-8028
Lee Cancer Care of Lee Memorial Health System Fort Myers, Florida  33901
Nemours Children's Clinic - Orlando Orlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando, Florida  32803-1273
St. Joseph's Cancer Institute at St. Joseph's Hospital Tampa, Florida  33607
Blank Children's Hospital Des Moines, Iowa  50309
Hackensack University Medical Center Cancer Center Hackensack, New Jersey  07601
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Presbyterian Cancer Center at Presbyterian Hospital Charlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Rainbow Babies and Children's Hospital Cleveland, Ohio  44106-5000
Rhode Island Hospital Comprehensive Cancer Center Providence, Rhode Island  02903
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Providence Cancer Center at Sacred Heart Medical Center Spokane, Washington  99220-2555
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
Childrens Hospital Los Angeles Los Angeles, California  90027
Rady Children's Hospital - San Diego San Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Alfred I. duPont Hospital for Children Wilmington, Delaware  19803
Mountain States Tumor Institute at St. Luke's Regional Medical Center Boise, Idaho  83712-6297
University of Illinois Cancer Center Chicago, Illinois  60612-7243
Tulane Cancer Center Office of Clinical Research Alexandria, Louisiana  71315-3198
C.S. Mott Children's Hospital at University of Michigan Medical Center Ann Arbor, Michigan  48109-0286
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
CCOP - Nevada Cancer Research Foundation Las Vegas, Nevada  89109-2306
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center New York, New York  10032
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Oklahoma University Cancer Institute Oklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science University Portland, Oregon  97239-3098
Geisinger Cancer Institute at Geisinger Health Danville, Pennsylvania  17822-0001
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Virginia Commonwealth University Massey Cancer Center Richmond, Virginia  23298-0037
Riley's Children Cancer Center at Riley Hospital for Children Indianapolis, Indiana  46202-5225
UAB Comprehensive Cancer Center Birmingham, Alabama  35294
University of Miami Sylvester Comprehensive Cancer Center - Miami Miami, Florida  33136
Lehigh Valley Hospital - Muhlenberg Bethlehem, Pennsylvania  18017
Duke Cancer Institute Durham, North Carolina  27710
Connecticut Children's Medical Center Hartford, Connecticut  06106
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum Health Grand Rapids, Michigan  49503
Legacy Emanuel Children's Hospital Portland, Oregon  97227