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 currently recruiting participants.
Verified July 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00716976
First received: July 15, 2008
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

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 compared with no additional treatment in preventing hearing loss in young patients receiving cisplatin for newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Liver Cancer
Neuroblastoma
Ototoxicity
Ovarian Cancer
Sarcoma
Drug: sodium thiosulfate
Procedure: examination
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of hearing loss [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]
  • Association of two key gene mutations (TPMT and COMT) with the development of cisplatin-induced hearing loss [ Designated as safety issue: No ]

Estimated Enrollment: 135
Study Start Date: June 2008
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: sodium thiosulfate
Given IV
Procedure: examination
Patients undergo audiological assessments periodically
No Intervention: Arm II (observation)
Patients do not receive sodium thiosulfate.
Procedure: examination
Patients undergo audiological assessments periodically

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.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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., 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 irradiation
  • Concurrent radiotherapy to extracranial sites allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00716976

  Show 77 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: David R. Freyer, DO, MS Children's Hospital Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Brad H. Pollock, Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00716976     History of Changes
Other Study ID Numbers: CDR0000588655, COG-ACCL0431
Study First Received: July 15, 2008
Last Updated: July 12, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Liver Neoplasms
Medulloblastoma
Nervous System Neoplasms
Neuroblastoma
Osteosarcoma
Ovarian Neoplasms
Central Nervous System Neoplasms
Neoplasms, Germ Cell and Embryonal
Hepatoblastoma
Sarcoma
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nervous System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases

ClinicalTrials.gov processed this record on May 16, 2013