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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00716976
First received: July 15, 2008
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Incidence of hearing loss [ Time Frame: 4 weeks after last dose of cisplatin ] [ Designated as safety issue: No ]
    Hearing loss is defined by comparing hearing sensitivity at follow up evaluation (4 weeks following the last dose of cisplatin) relative to baseline measurements using ASHA criteria. The proportion of patients treated with sodium thiosulfate who develop hearing loss will be compared with that of patients who did not receive the study drug.


Secondary Outcome Measures:
  • Change in hearing thresholds for key frequencies [ Time Frame: 4 weeks after last dose of cisplatin ] [ Designated as safety issue: No ]
    Change in hearing thresholds for key frequencies important for communication between baseline to the 4-week follow-up evaluation.

  • Event-free-survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Event free survival rate will be computed from time to study entry until disease relapse/progression, secondary malignancy, or death.

  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Overall survival rate is computed from time on study until death from any cause.

  • Hearing loss among patients carrying/not-carrying two key gene mutations (TPMT and COMT) [ Time Frame: 4 weeks after the last dose of cisplatin ] [ Designated as safety issue: No ]

Enrollment: 131
Study Start Date: June 2008
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Experimental: Observation Arm (No sodium thiosulfate treatment)
Patients do not receive sodium thiosulfate.
Procedure: examination
Patients undergo audiological assessments periodically

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.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00716976

  Hide Study Locations
Locations
United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Southern California Permanente Medical Group
Los Angeles, California, United States, 90027
Children's Hospital Central California
Madera, California, United States, 93638-8762
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123-4282
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Idaho
Mountain States Tumor Institute at St. Luke's Regional Medical Center
Boise, Idaho, United States, 83712-6297
United States, Illinois
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612-7243
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61603
United States, Indiana
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Louisiana
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, United States, 71315-3198
Children's Hospital of New Orleans
New Orleans, Louisiana, United States, 70118
United States, Maryland
National Naval Medical Center
Bethesda, Maryland, United States, 20889-5600
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109-0286
Hurley Medical Center
Flint, Michigan, United States, 48503
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007-5381
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Hospital
St. Louis, Missouri, United States, 63104
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89109-2306
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87131-5636
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205-2696
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
Legacy Emanuel Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, United States, 18017
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, United States, 17822-0001
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, South Dakota
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
United States, Texas
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78207
United States, Virginia
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507-1971
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Washington
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
United States, Wisconsin
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, British Columbia
Children's and Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1V 4G2
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: David R. Freyer, DO, MS Children's Hospital Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00716976     History of Changes
Other Study ID Numbers: ACCL0431, COG-ACCL0431, CDR0000588655
Study First Received: July 15, 2008
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
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

Additional relevant MeSH terms:
Brain Neoplasms
Liver Neoplasms
Medulloblastoma
Nervous System Neoplasms
Neuroblastoma
Osteosarcoma
Ovarian Neoplasms
Central Nervous System Neoplasms
Neoplasms, Germ Cell and Embryonal
Hepatoblastoma
Sarcoma
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on August 26, 2014