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

Children's Oncology Group

Status and phase

Completed

Phase 3

Conditions

Sarcoma

Neuroblastoma

Extragonadal Germ Cell Tumor

Brain Tumor

Central Nervous System Tumor

Childhood Germ Cell Tumor

Ototoxicity

Ovarian Cancer

Liver Cancer

Treatments

Drug: sodium thiosulfate

Procedure: examination

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00716976

ACCL0431

CDR0000588655 (Other Identifier)

COG-ACCL0431 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

131 patients

Sex

All

Ages

1 to 18 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Supportive Care

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

131 participants in 2 patient groups

STS Arm (sodium thiosulfate treatment)

Experimental group

Description:

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.

Treatment:

Drug: sodium thiosulfate

Procedure: examination

Observation Arm (No sodium thiosulfate treatment)

Experimental group

Description:

Patients do not receive sodium thiosulfate.

Treatment:

Procedure: examination