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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00716976
First received: July 15, 2008
Last updated: April 15, 2014
Last verified: April 2014

July 15, 2008
April 15, 2014
June 2008
September 2012   (final data collection date for primary outcome measure)
Incidence of hearing loss [ Time Frame: 4 weeks after last dose of cisplatin ] [ Designated as safety issue: No ]
Hearing loss is defined by comparing hearing sensitivity at follow up evaluation (4 weeks following the last dose of cisplatin) relative to baseline measurements using ASHA criteria. The proportion of patients treated with sodium thiosulfate who develop hearing loss will be compared with that of patients who did not receive the study drug.
Incidence of hearing loss [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00716976 on ClinicalTrials.gov Archive Site
  • Change in hearing thresholds for key frequencies [ Time Frame: 4 weeks after last dose of cisplatin ] [ Designated as safety issue: No ]
    Change in hearing thresholds for key frequencies important for communication between baseline to the 4-week follow-up evaluation.
  • Event-free-survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Event free survival rate will be computed from time to study entry until disease relapse/progression, secondary malignancy, or death.
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Overall survival rate is computed from time on study until death from any cause.
  • Hearing loss among patients carrying/not-carrying two key gene mutations (TPMT and COMT) [ Time Frame: 4 weeks after the last dose of cisplatin ] [ Designated as safety issue: No ]
  • Mean change in hearing thresholds for key frequencies [ Designated as safety issue: No ]
  • Incidences of cisplatin-related grade 3 and 4 nephrotoxicity and grade 3 and 4 cytopenia [ Designated as safety issue: Yes ]
  • Event-free-survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
  • Brain Tumor
  • Central Nervous System Tumor
  • Childhood Germ Cell Tumor
  • Extragonadal Germ Cell Tumor
  • Liver Cancer
  • Neuroblastoma
  • Ototoxicity
  • Ovarian Cancer
  • Sarcoma
  • Drug: sodium thiosulfate
    Given IV
    Other Names:
    • ADH300001
    • Disodium Thiosulfate Pentahydrate
    • Na Thiosulfate
    • Sodium Hyposulfite
    • Sodium Thiosulphate
    • Thiosulfuric Acid
    • Disodium Salt
    • Pentahydrate
    • Versiclear
    • NSC# 45624
    • IND#72877
  • Procedure: examination
    Patients undergo audiological assessments periodically
  • 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.
    Interventions:
    • Drug: sodium thiosulfate
    • Procedure: examination
  • Experimental: Observation Arm (No sodium thiosulfate treatment)
    Patients do not receive sodium thiosulfate.
    Intervention: Procedure: examination
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
131
Not Provided
September 2012   (final data collection date for primary outcome measure)

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.
Both
1 Year to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Australia
 
NCT00716976
ACCL0431, COG-ACCL0431, CDR0000588655
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: David R. Freyer, DO, MS Children's Hospital Los Angeles
Children's Oncology Group
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP