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
  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 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 Tumor
Central Nervous System Tumor
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
Intervention Model: Parallel Assignment
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 Children's Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 131
Study Start Date: June 2008
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: Observation Arm (No sodium thiosulfate treatment)
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., 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00716976

  Show 76 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: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00716976     History of Changes
Other Study ID Numbers: ACCL0431, COG-ACCL0431, CDR0000588655
Study First Received: July 15, 2008
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
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:
Neoplasms
Ovarian Neoplasms
Neuroblastoma
Neoplasms, Germ Cell and Embryonal
Liver Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Osteosarcoma
Medulloblastoma
Hepatoblastoma
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on September 18, 2014