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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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ClinicalTrials.gov Identifier: NCT00716976
Recruitment Status : Completed
First Posted : July 16, 2008
Results First Posted : June 1, 2017
Last Update Posted : September 20, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE July 15, 2008
First Posted Date  ICMJE July 16, 2008
Results First Submitted Date  ICMJE December 9, 2016
Results First Posted Date  ICMJE June 1, 2017
Last Update Posted Date September 20, 2018
Study Start Date  ICMJE June 2008
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2008)
Incidence of Hearing Loss
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • Overall Survival (OS) [ Time Frame: 4 Years after enrollment ]
    Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
  • Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT) [ Time Frame: 4 weeks after the last dose of cisplatin ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2008)
  • Mean change in hearing thresholds for key frequencies
  • Incidences of cisplatin-related grade 3 and 4 nephrotoxicity and grade 3 and 4 cytopenia
  • Event-free-survival
  • Overall survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
Official Title  ICMJE A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children
Brief Summary

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

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Brain Tumor
  • Central Nervous System Tumor
  • Childhood Germ Cell Tumor
  • Extragonadal Germ Cell Tumor
  • Liver Cancer
  • Neuroblastoma
  • Ototoxicity
  • Ovarian Cancer
  • Sarcoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * 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. Erratum in: Lancet Oncol. 2017 Jun;18(6):e301.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 24, 2013)
131
Original Enrollment  ICMJE
 (submitted: July 15, 2008)
120
Actual Study Completion Date  ICMJE April 9, 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00716976
Other Study ID Numbers  ICMJE ACCL0431
COG-ACCL0431 ( Other Identifier: Children's Oncology Group )
CDR0000588655 ( Other Identifier: Clinical Trials.gov )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: David R. Freyer, DO, MS Children's Hospital Los Angeles
PRS Account Children's Oncology Group
Verification Date August 2018

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