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 : July 6, 2021
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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 or disease||Intervention/treatment||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|
- 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.
- 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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||131 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (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|
|Actual Study Start Date :||June 23, 2008|
|Actual Primary Completion Date :||April 9, 2015|
|Actual Study Completion Date :||June 30, 2021|
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
Patients undergo audiological assessments periodically
Experimental: Observation Arm (No sodium thiosulfate treatment)
Patients do not receive sodium thiosulfate.
Patients undergo audiological assessments periodically
- 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.
- 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 ]
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|Ages Eligible for Study:||1 Year to 18 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00716976
|Study Chair:||David R. Freyer, DO, MS||Children's Hospital Los Angeles|
|Responsible Party:||Children's Oncology Group|
|Other Study ID Numbers:||
COG-ACCL0431 ( Other Identifier: Children's Oncology Group )
CDR0000588655 ( Other Identifier: Clinical Trials.gov )
|First Posted:||July 16, 2008 Key Record Dates|
|Results First Posted:||June 1, 2017|
|Last Update Posted:||July 6, 2021|
|Last Verified:||July 2021|
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
localized resectable neuroblastoma
localized unresectable neuroblastoma
stage 4S neuroblastoma
stage I childhood liver cancer
stage II childhood liver cancer
stage III childhood liver cancer
stage IV childhood liver cancer
Neoplasms, Germ Cell and Embryonal
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Nervous System Diseases
Digestive System Neoplasms
Digestive System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Complex and Mixed