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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, Supportive careClosed1 to 18NCI, OtherACCL0431
COG-ACCL0431, CDR0000588655, NCT00716976

Trial Description


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.

Further Study Information



  • 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.


  • 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.

Eligibility 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 hours
  • 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., 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.

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

  • National Cancer Institute
David Robert Freyer, Study Chair

Trial Sites


Palo Alto

Lucile Packard Children's Hospital at Stanford University Medical Center

Neyssa M Marina
Ph: 650-498-7061


Cleveland Clinic Taussig Cancer Center

Tanya M Tekautz
Ph: 866-223-8100



Children's Hospital of Eastern Ontario

Jacqueline M Halton
Ph: 613-738-3931

Link to the current record.
NLM Identifier NCT00716976 processed this data on April 09, 2015

Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to