Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Ear, Nose, and Throat Diseases

Nervous System Diseases

Symptoms and General Pathology

Digestive System Diseases

Substance Related Disorders

Wounds and Injuries

Skin and Connective Tissue Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hearing Loss

Deafness

Liver Neoplasms

Sarcoma

Teratoma

Brain Neoplasms

Osteosarcoma

Central Nervous System Neoplasms

Medulloblastoma

Neuroblastoma

Testicular Neoplasms

Nervous System Neoplasms

Ototoxicity

Hepatoblastoma

Neoplasms, Germ Cell and Embryonal

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Glioma

Ear Diseases

Otorhinolaryngologic Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Germ Cells Tumors

Ovarian Germ Cell Tumor

Testicular Germ Cell Tumor

Medulloblastoma, Childhood

Extragonadal Germ Cell Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Anti-Infective Agents

Cisplatin

Liver Extracts

Sodium thiosulfate

Antidotes

Protective Agents

Antioxidants

Antitubercular Agents

Anti-Bacterial Agents

Chelating Agents

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.

Patients do not receive sodium thiosulfate.

sodium thiosulfate

Patients undergo audiological assessments periodically

examination

David R. Freyer, DO, MS

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.

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.

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 Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children

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

Mean change in hearing threshold (post-pre) at 500 hz.

Mean change in hearing threshold (post-pre) at 1000 hz.

Mean change in hearing threshold (post-pre) at 2000 hz

Mean change in hearing threshold (post-pre) at 4000 hz.

Mean change in hearing threshold (post-pre) at 8000 hz.

Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.

Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.

National Cancer Institute (NCI)

Children's Oncology Group

Serious Adverse Events were reported on this study via the NCI AERS reporting system. Per protocol, no expedited reports were submitted for patients on Observation only arm of the study. Thus, no patients enrolled on the Observation arm of the trial were at risk for having a Serious Adverse Event reported.

STS Arm (Sodium Thiosulfate Treatment)

Observation Arm

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

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 Reporting Coordinator

55 eligible patients enrolled on the observation Arm had complete audiometry data for evaluation; 49 eligible patients enrolled on the STS arm had complete data audiometry for evaluation.

Incidence of Hearing Loss

38 eligible patients in the STS arm had paired audiometry at 500 hz; 45 patients in the observation arm had paired audiometry at 500 hz.

Change in Hearing Thresholds For Key Frequencies at 500 hz

37 eligible patients in the STS arm had paired audiometry at 1000 hz; 47 patients in the observation arm had paired audiometry at 1000 hz.

Change in Hearing Thresholds For Key Frequencies at 1000 hz

38 eligible patients in the STS arm had paired audiometry at 2000 hz; 47 patients in the observation arm had paired audiometry at 2000 hz.

Change in Hearing Thresholds For Key Frequencies at 2000 hz

38 eligible patients in the STS arm had paired audiometry at 4000 hz; 47 patients in the observation arm had paired audiometry at 4000 hz.

Change in Hearing Thresholds For Key Frequencies at 4000 hz

38 eligible patients in the STS arm had paired audiometry at 8000 hz; 42 patients in the observation arm had paired audiometry at 8000 hz.

Change in Hearing Thresholds For Key Frequencies at 8000 hz

61 eligible patients were enrolled on the STS arm; 64 eligible patients were enrolled on the observation arm.

Event-Free Survival (EFS)

Overall Survival (OS)

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.

sodium thiosulfate: Given IV

examination: Patients undergo audiological assessments periodically

Patients do not receive sodium thiosulfate.

examination: Patients undergo audiological assessments periodically

Observation Arm (No Sodium Thiosulfate Treatment)

Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)

Overall Study

Diseases and Abnormalities at or Before Birth

Respiratory Tract (Lung and Bronchial) Diseases

Syndrome

Carcinoma, Renal Cell

Wilms Tumor

Kidney Neoplasms

Rhabdomyosarcoma

Pulmonary Blastoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Renal Cell Carcinoma

Wilms' Tumor

Pleuropulmonary Blastoma

DNA analysis

cytogenetic analysis

gene expression analysis

gene rearrangement analysis

mutation analysis

polymerase chain reaction

polymorphism analysis

laboratory biomarker analysis

medical chart review

Dana A. Hill, MD

RATIONALE: The identification of gene mutations in young patients with pleuropulmonary blastoma syndrome may allow doctors to better understand the genetic processes involved in the development of some types of cancer, and may also help doctors identify patients who are at risk for cancer.

PURPOSE: This research study studies gene mutations in samples from young patients with pleuropulmonary blastoma syndrome at risk for developing cancer.

OBJECTIVES:

* To determine if DICER1 mutations contribute to tumor pathogenesis in cystic nephromas and cystic partially differentiated nephroblastomas outside of families with pleuropulmonary blastoma (PPB) syndrome.

OUTLINE: Archived DNA samples are analyzed for DICER1 mutation by qPCR and directly sequenced using BigDye Terminator chemistry. Results are then compared against the single nucleotide polymorphism (SNP) database.

Gene Mutation in Samples From Young Patients With Pleuropulmonary Blastoma Syndrome at Risk for Developing Cancer

Investigation of DICER1 in Cystic Nephroma and Cystic Partially Differentiated Nephroblastoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	Brain Tumor Central Nervous... Childhood Germ ... Extragonadal Ge... Liver Cancer Neuroblastoma Ototoxicity Ovarian Cancer Sarcoma	sodium thiosulf... examination	1 Year - 18 Years	Children's Oncology Group
Gene Mutation in Samples From Young Patients With Pleuropulmonary Blastoma Syndrome at Risk for Developing Cancer	NCT01353300	Brain and Centr... Hereditary Wilm... Kidney Cancer Liver Cancer Neuroblastoma Pleuropulmonary... Sarcoma	DNA analysis cytogenetic ana... gene expression... gene rearrangem... mutation analys... polymerase chai... polymorphism an... laboratory biom... medical chart r...	- 120 Years	Children's Oncology Group

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