Brain TumorPhase 3NCT00716976
Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
A Phase 3 study testing sodium thiosulfate and examination in people with Brain Tumor and Central Nervous System Tumor, run by Children's Oncology Group at 76 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Brain Tumor, Central Nervous System Tumor, Childhood Germ Cell Tumor
- What is being tested?
- sodium thiosulfate and examination
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 76 sitesin 3 countries
- Study dates
- 23 Jun 2008to 30 Jun 2021
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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 locations and contacts
76 sites in 3 countries.
76 sites in 3 countries
United States68 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87131-5636
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, 71315-3198
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, 48109-0286
National Naval Medical Center
Bethesda, Maryland, 20889-5600
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294
Mountain States Tumor Institute at St. Luke's Regional Medical Center
Boise, Idaho, 83712-6297
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, 28233-3549
University of Illinois Cancer Center
Chicago, Illinois, 60612-7243
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106-5000
Nationwide Children's Hospital
Columbus, Ohio, 43205-2696
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, 17822-0001
Blank Children's Hospital
Des Moines, Iowa, 50309
Duke Cancer Institute
Durham, North Carolina, 27710
Hurley Medical Center
Flint, Michigan, 48503
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, 33901
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54307-3508
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Cancer Research Center of Hawaii
Honolulu, Hawaii, 96813
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, 46202
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, 52242-1002
Nemours Children's Clinic
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007-5381
Children's Mercy Hospital
Kansas City, Missouri, 64108
East Tennessee Children's Hospital
Knoxville, Tennessee, 37916
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, 89109-2306
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Childrens Hospital Los Angeles
Los Angeles, California, 90027
Southern California Permanente Medical Group
Los Angeles, California, 90027
Kosair Children's Hospital
Louisville, Kentucky, 40232
Children's Hospital Central California
Madera, California, 93638-8762
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, 33136
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
Yale Cancer Center
New Haven, Connecticut, 06520-8028
Children's Hospital of New Orleans
New Orleans, Louisiana, 70118
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, 10032
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507-1971
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, 73104
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, 32803-1273
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Jude Midwest Affiliate
Peoria, Illinois, 61603
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15213
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, 97239-3098
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, 02903
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298-0037
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78207
Rady Children's Hospital - San Diego
San Diego, California, 92123-4282
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, 57117-5039
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, 99220-2555
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
All Children's Hospital
St. Petersburg, Florida, 33701
SUNY Upstate Medical University Hospital
Syracuse, New York, 13210
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, 33607
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
Canada7 sites
IWK Health Centre
Halifax, Nova Scotia, B3J 3G9
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Centre Hospitalier Universitaire de Quebec
Québec, G1V 4G2
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, S7N 4H4
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Children's and Women's Hospital of British Columbia
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Australia1 site
Princess Margaret Hospital for Children
Perth, Western Australia, 6001
About this study
Official title: A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children
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.
Read the 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.
- Conditions
- Brain Tumor, Central Nervous System Tumor, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor, Liver Cancer, Neuroblastoma
- Being tested
- sodium thiosulfate, examination
- Keywords
- ototoxicity, 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, childhood teratoma, childhood medulloblastoma, disseminated neuroblastoma, regional neuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, stage 4S neuroblastoma, localized osteosarcoma, metastatic osteosarcoma, childhood hepatoblastoma, stage I childhood liver cancer, stage II childhood liver cancer, stage III childhood liver cancer, stage IV childhood liver cancer
- Medical subject headings
- Brain Neoplasms, Central Nervous System Neoplasms, Liver Neoplasms, Neuroblastoma, Ototoxicity, Ovarian Neoplasms, Sarcoma, Testicular Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium thiosulfateDrug
Also called ADH300001, Disodium Thiosulfate Pentahydrate, Na Thiosulfate, Sodium Hyposulfite
Given IV
examinationProcedure or surgery
Patients undergo audiological assessments periodically
| Study group | Role | What they receive |
|---|---|---|
| STS Arm (sodium thiosulfate treatment) | Experimental | 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. Receives: Drug: sodium thiosulfate; Procedure: examination |
| Observation Arm (No sodium thiosulfate treatment) | Experimental | Patients do not receive sodium thiosulfate. Receives: Procedure: examination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Hearing Loss
Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
Measured: 4 weeks after last dose of cisplatin
Secondary outcomes (8)
Change in Hearing Thresholds For Key Frequencies at 500 hz
Mean change in hearing threshold (post-pre) at 500 hz.
Measured: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 1000 hz
Mean change in hearing threshold (post-pre) at 1000 hz.
Measured: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 2000 hz
Mean change in hearing threshold (post-pre) at 2000 hz
Measured: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 4000 hz
Mean change in hearing threshold (post-pre) at 4000 hz.
Measured: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 8000 hz
Mean change in hearing threshold (post-pre) at 8000 hz.
Measured: 4 weeks after last dose of cisplatin
Event-Free Survival (EFS)
Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Measured: 4 years after enrollment
Overall Survival (OS)
Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Measured: 4 Years after enrollment
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
Measured: 4 weeks after the last dose of cisplatin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2008 (estimated)
- Study start23 Jun 2008
- Primary completion9 Apr 2015
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain TumorStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David R. Freyer, DO, MS, Study chair, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00716976
- Sponsor's protocol ID
- ACCL0431
- Other IDs
- COG-ACCL0431, CDR0000588655
- Status last verified
- Jul 2021
- First submitted
- 15 Jul 2008
- Last updated
- 9 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 27914822