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

NCT00716976 | Completed Phase 3 Results DMC

• 3 other identifiers: ACCL0431COG-ACCL0431CDR0000588655
• Study Type: interventional
• Target: 131
• Locations: 3 countries
• Sites: 76

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Hearing Loss

  Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.

  4 weeks after last dose of cisplatin

Secondary Outcomes (8)

• Change in Hearing Thresholds For Key Frequencies at 500 hz

  4 weeks after last dose of cisplatin

• Change in Hearing Thresholds For Key Frequencies at 1000 hz

  4 weeks after last dose of cisplatin

• Change in Hearing Thresholds For Key Frequencies at 2000 hz

  4 weeks after last dose of cisplatin

• Change in Hearing Thresholds For Key Frequencies at 4000 hz

  4 weeks after last dose of cisplatin

• Change in Hearing Thresholds For Key Frequencies at 8000 hz

  4 weeks after last dose of cisplatin

Study Arms (2)

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.

Drug: sodium thiosulfate; Procedure: examination

Observation Arm (No sodium thiosulfate treatment)

EXPERIMENTAL

Patients do not receive sodium thiosulfate.

Procedure: examination

Interventions

sodium thiosulfate DRUG

Given IV

Also known as: ADH300001, Disodium Thiosulfate Pentahydrate, Na Thiosulfate, Sodium Hyposulfite, Sodium Thiosulphate, Thiosulfuric Acid, Disodium Salt, Pentahydrate, Versiclear, NSC# 45624, IND#72877

STS Arm (sodium thiosulfate treatment)

examination PROCEDURE

Patients undergo audiological assessments periodically

Observation Arm (No sodium thiosulfate treatment); STS Arm (sodium thiosulfate treatment)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (76)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Southern California Permanente Medical Group

Los Angeles, California, 90027, United States

Location

Children's Hospital Central California

Madera, California, 93638-8762, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123-4282, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

Nemours Children's Clinic - Orlando

Orlando, Florida, 32806, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, 33607, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, 83712-6297, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612-7243, United States

Location

Saint Jude Midwest Affiliate

Peoria, Illinois, 61603, United States

Location

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, 71315-3198, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

National Naval Medical Center

Bethesda, Maryland, 20889-5600, United States

Location

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, 48109-0286, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007-5381, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89109-2306, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, 28233-3549, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106-5000, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States

Location

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18017, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, 02903, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37916, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507-1971, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99220-2555, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Children's and Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3J 3G9, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Central Nervous System Neoplasms; Liver Neoplasms; Neuroblastoma; Ototoxicity; Ovarian Neoplasms; Sarcoma; Testicular Neoplasms; Ovarian Germ Cell Cancer; Teratoma; Medulloblastoma; Osteosarcoma; Hepatoblastoma

Interventions

sodium thiosulfate; Restraint, Physical

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Ear Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Genital Neoplasms, Male; Genital Diseases, Male; Male Urogenital Diseases; Testicular Diseases; Glioma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques

Limitations and Caveats

Data was and never will be collected for Outcome Measure #9, Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT).

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• David R. Freyer, DO, MS

  Children's Hospital Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2008
• First Posted: July 16, 2008
• Study Start: June 23, 2008
• Primary Completion: April 9, 2015
• Study Completion: June 30, 2021
• Last Updated: November 9, 2023
• Results First Posted: June 1, 2017

Record last verified: 2021-07

Locations

US (68); AU (1); CA (7)