TriangleNCT00716976 · CITED IN SOURCE DOCUMENTS
Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2023-11-09
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.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Incidence of Hearing Loss
Change in Hearing Thresholds For Key Frequencies at 500 hz
Change in Hearing Thresholds For Key Frequencies at 1000 hz
Change in Hearing Thresholds For Key Frequencies at 2000 hz
Change in Hearing Thresholds For Key Frequencies at 4000 hz
Change in Hearing Thresholds For Key Frequencies at 8000 hz
Event-Free Survival (EFS)
Overall Survival (OS)
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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.
- healthy Volunteers
- false
- maximum Age
- 18 Years
- minimum Age
- 1 Year
- sex
- ALL
- std Ages
- CHILD
- ADULT
Treatment arms and interventions
- arm Groups
- 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.
- intervention Names
- Drug: sodium thiosulfate
- Procedure: examination
- label
- STS Arm (sodium thiosulfate treatment)
- type
- EXPERIMENTAL
- description
- Patients do not receive sodium thiosulfate.
- intervention Names
- Procedure: examination
- label
- Observation Arm (No sodium thiosulfate treatment)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- STS Arm (sodium thiosulfate treatment)
- description
- Given IV
- name
- sodium thiosulfate
- other Names
- ADH300001
- Disodium Thiosulfate Pentahydrate
- Na Thiosulfate
- Sodium Hyposulfite
- Sodium Thiosulphate
- Thiosulfuric Acid
- Disodium Salt
- Pentahydrate
- Versiclear
- NSC# 45624
- IND#72877
- type
- DRUG
- arm Group Labels
- Observation Arm (No sodium thiosulfate treatment)
- STS Arm (sodium thiosulfate treatment)
- description
- Patients undergo audiological assessments periodically
- name
- examination
- type
- PROCEDURE
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- SUPPORTIVE_CARE
Enrollment
- count
- 131
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
- measure
- Incidence of Hearing Loss
- time Frame
- 4 weeks after last dose of cisplatin
- secondary Outcomes
- description
- Mean change in hearing threshold (post-pre) at 500 hz.
- measure
- Change in Hearing Thresholds For Key Frequencies at 500 hz
- time Frame
- 4 weeks after last dose of cisplatin
- description
- Mean change in hearing threshold (post-pre) at 1000 hz.
- measure
- Change in Hearing Thresholds For Key Frequencies at 1000 hz
- time Frame
- 4 weeks after last dose of cisplatin
- description
- Mean change in hearing threshold (post-pre) at 2000 hz
- measure
- Change in Hearing Thresholds For Key Frequencies at 2000 hz
- time Frame
- 4 weeks after last dose of cisplatin
- description
- Mean change in hearing threshold (post-pre) at 4000 hz.
- measure
- Change in Hearing Thresholds For Key Frequencies at 4000 hz
- time Frame
- 4 weeks after last dose of cisplatin
- description
- Mean change in hearing threshold (post-pre) at 8000 hz.
- measure
- Change in Hearing Thresholds For Key Frequencies at 8000 hz
- time Frame
- 4 weeks after last dose of cisplatin
- description
- Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
- measure
- Event-Free Survival (EFS)
- time Frame
- 4 years after enrollment
- description
- Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
- measure
- Overall Survival (OS)
- time Frame
- 4 Years after enrollment
- measure
- Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
- time Frame
- 4 weeks after the last dose of cisplatin
Full study description
- brief Summary
- 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.
- 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.
Source references
- references
- citation
- Freyer DR, Chen L, Krailo MD, Knight K, Villaluna D, Bliss B, Pollock BH, Ramdas J, Lange B, Van Hoff D, VanSoelen ML, Wiernikowski J, Neuwelt EA, Sung L. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jan;18(1):63-74. doi: 10.1016/S1470-2045(16)30625-8. Epub 2016 Dec 1.
- pmid
- 27914822
- type
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Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice