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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00716976

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 III

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:

Genetics Home Reference related topics: neuroblastoma nonsyndromic deafness Pendred syndrome

MedlinePlus related topics: Cancer Hearing Disorders and Deafness Liver Cancer Neuroblastoma Ovarian Cancer Soft Tissue Sarcoma

Drug Information available for: Sodium thiosulfate Cisplatin Sodium hyposulfite

U.S. FDA Resources

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 79 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

David R. Freyer, DO, MS

Children's Hospital Los Angeles

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	February 5, 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 February 09, 2012