The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00716976




Registration number
NCT00716976
Ethics application status
Date submitted
15/07/2008
Date registered
16/07/2008
Date last updated
20/09/2018

Titles & IDs
Public 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
Scientific title
A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children
Secondary ID [1] 0 0
COG-ACCL0431
Secondary ID [2] 0 0
ACCL0431
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Tumor 0 0
Central Nervous System Tumor 0 0
Childhood Germ Cell Tumor 0 0
Extragonadal Germ Cell Tumor 0 0
Liver Cancer 0 0
Neuroblastoma 0 0
Ototoxicity 0 0
Ovarian Cancer 0 0
Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Liver
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - sodium thiosulfate
Treatment: Surgery - examination

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.

Experimental: Observation Arm (No sodium thiosulfate treatment) - Patients do not receive sodium thiosulfate.


Treatment: Drugs: sodium thiosulfate
Given IV

Treatment: Surgery: examination
Patients undergo audiological assessments periodically

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Hearing Loss - Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
Timepoint [1] 0 0
4 weeks after last dose of cisplatin
Secondary outcome [1] 0 0
Change in Hearing Thresholds For Key Frequencies at 500 hz - Mean change in hearing threshold (post-pre) at 500 hz.
Timepoint [1] 0 0
4 weeks after last dose of cisplatin
Secondary outcome [2] 0 0
Change in Hearing Thresholds For Key Frequencies at 1000 hz - Mean change in hearing threshold (post-pre) at 1000 hz.
Timepoint [2] 0 0
4 weeks after last dose of cisplatin
Secondary outcome [3] 0 0
Change in Hearing Thresholds For Key Frequencies at 2000 hz - Mean change in hearing threshold (post-pre) at 2000 hz
Timepoint [3] 0 0
4 weeks after last dose of cisplatin
Secondary outcome [4] 0 0
Change in Hearing Thresholds For Key Frequencies at 4000 hz - Mean change in hearing threshold (post-pre) at 4000 hz.
Timepoint [4] 0 0
4 weeks after last dose of cisplatin
Secondary outcome [5] 0 0
Change in Hearing Thresholds For Key Frequencies at 8000 hz - Mean change in hearing threshold (post-pre) at 8000 hz.
Timepoint [5] 0 0
4 weeks after last dose of cisplatin
Secondary outcome [6] 0 0
Event-Free Survival (EFS) - Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Timepoint [6] 0 0
4 years after enrollment
Secondary outcome [7] 0 0
Overall Survival (OS) - Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Timepoint [7] 0 0
4 Years after enrollment
Secondary outcome [8] 0 0
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
Timepoint [8] 0 0
4 weeks after the last dose of cisplatin

Eligibility
Key inclusion 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.
Minimum age
1 Year
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Supportive Care
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Hawaii
Country [9] 0 0
United States of America
State/province [9] 0 0
Idaho
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Iowa
Country [13] 0 0
United States of America
State/province [13] 0 0
Kentucky
Country [14] 0 0
United States of America
State/province [14] 0 0
Louisiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Maryland
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Minnesota
Country [18] 0 0
United States of America
State/province [18] 0 0
Missouri
Country [19] 0 0
United States of America
State/province [19] 0 0
Nevada
Country [20] 0 0
United States of America
State/province [20] 0 0
New Jersey
Country [21] 0 0
United States of America
State/province [21] 0 0
New Mexico
Country [22] 0 0
United States of America
State/province [22] 0 0
New York
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Ohio
Country [25] 0 0
United States of America
State/province [25] 0 0
Oklahoma
Country [26] 0 0
United States of America
State/province [26] 0 0
Oregon
Country [27] 0 0
United States of America
State/province [27] 0 0
Pennsylvania
Country [28] 0 0
United States of America
State/province [28] 0 0
Rhode Island
Country [29] 0 0
United States of America
State/province [29] 0 0
South Dakota
Country [30] 0 0
United States of America
State/province [30] 0 0
Tennessee
Country [31] 0 0
United States of America
State/province [31] 0 0
Texas
Country [32] 0 0
United States of America
State/province [32] 0 0
Virginia
Country [33] 0 0
United States of America
State/province [33] 0 0
Washington
Country [34] 0 0
United States of America
State/province [34] 0 0
Wisconsin
Country [35] 0 0
Canada
State/province [35] 0 0
British Columbia
Country [36] 0 0
Canada
State/province [36] 0 0
Manitoba
Country [37] 0 0
Canada
State/province [37] 0 0
Nova Scotia
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Canada
State/province [40] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00716976
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David R. Freyer, DO, MS
Address 0 0
Children's Hospital Los Angeles
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications