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

• ClinicalTrials.gov Identifier: NCT00716976
• Recruitment Status: Completed
• First Posted: July 16, 2008
• Results First Posted: June 1, 2017
• Last Update Posted: November 9, 2023
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Tracking Information

• First Submitted Date: July 15, 2008
• First Posted Date: July 16, 2008
• Results First Submitted Date: December 9, 2016
• Results First Posted Date: June 1, 2017
• Last Update Posted Date: November 9, 2023
• Actual Study Start Date: June 23, 2008
• Actual Primary Completion Date: April 9, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 1, 2017)

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.

• Original Primary Outcome Measures (submitted: July 15, 2008): Incidence of hearing loss

Current Secondary Outcome Measures (submitted: June 27, 2017)

• 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 ]

Original Secondary Outcome Measures (submitted: July 15, 2008)

• Mean change in hearing thresholds for key frequencies
• Incidences of cisplatin-related grade 3 and 4 nephrotoxicity and grade 3 and 4 cytopenia
• Event-free-survival
• Overall survival

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
• Official Title: A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care

Condition

• Brain Tumor
• Central Nervous System Tumor
• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Liver Cancer
• Neuroblastoma
• Ototoxicity
• Ovarian Cancer
• Sarcoma

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Drug: sodium thiosulfate
  • Procedure: examination
• Experimental: Observation Arm (No sodium thiosulfate treatment)
  Patients do not receive sodium thiosulfate.
  Intervention: Procedure: examination

• Publications *: 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. Erratum In: Lancet Oncol. 2017 Jun;18(6):e301.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 24, 2013): 131
• Original Enrollment (submitted: July 15, 2008): 120
• Actual Study Completion Date: June 30, 2021
• Actual Primary Completion Date: April 9, 2015 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT00716976
• Other Study ID Numbers: ACCL0431; COG-ACCL0431 ( Other Identifier: Children's Oncology Group ); CDR0000588655 ( Other Identifier: Clinical Trials.gov )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Children's Oncology Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: Children's Oncology Group
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: David R. Freyer, DO, MS; Children's Hospital Los Angeles

• PRS Account: Children's Oncology Group
• Verification Date: July 2021