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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00716976

Enrollment

131

Registered

2008-07-16

Start date

2008-06-23

Completion date

2021-06-30

Last updated

2023-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

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.

Interventions

DRUGsodium thiosulfate

Given IV

PROCEDUREexamination

Patients undergo audiological assessments periodically

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

1 Years to 18 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Hearing Loss	4 weeks after last dose of cisplatin	Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.

Secondary

Measure	Time frame	Description
Change in Hearing Thresholds For Key Frequencies at 4000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 4000 hz.
Change in Hearing Thresholds For Key Frequencies at 8000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 8000 hz.
Event-Free Survival (EFS)	4 years after enrollment	Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Overall Survival (OS)	4 Years after enrollment	Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Change in Hearing Thresholds For Key Frequencies at 1000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 1000 hz.
Change in Hearing Thresholds For Key Frequencies at 2000 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 2000 hz
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)	4 weeks after the last dose of cisplatin	—
Change in Hearing Thresholds For Key Frequencies at 500 hz	4 weeks after last dose of cisplatin	Mean change in hearing threshold (post-pre) at 500 hz.

Countries

Australia, Canada, United States

Participant flow

Participants by arm

Arm	Count
STS Arm (Sodium Thiosulfate Treatment) Sodium thiosulfate treatment.	65
Observation Arm No sodium thiosulfate treatment.	66
Total	131

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	0
Overall Study	Death	1	0
Overall Study	Ineligibles	4	2
Overall Study	Physician Decision	2	2
Overall Study	Premature discontinuation cisplatin	5	4
Overall Study	Radiation during protocol	1	0
Overall Study	Withdrawal by Subject	5	1

Baseline characteristics

Characteristic	STS Arm (Sodium Thiosulfate Treatment)	Observation Arm	Total
Age, Categorical <=18 years	65 Participants	66 Participants	131 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	8.97 Years STANDARD_DEVIATION 5.93	8.39 Years STANDARD_DEVIATION 5.88	8.68 Years STANDARD_DEVIATION 5.89
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants	15 Participants	34 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants	48 Participants	92 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	3 Participants	5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	3 Participants
Race (NIH/OMB) Black or African American	7 Participants	10 Participants	17 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants	12 Participants	23 Participants
Race (NIH/OMB) White	44 Participants	41 Participants	85 Participants
Region of Enrollment Canada	8 participants	4 participants	12 participants
Region of Enrollment United States	56 participants	62 participants	118 participants
Sex: Female, Male Female	27 Participants	24 Participants	51 Participants
Sex: Female, Male Male	38 Participants	42 Participants	80 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	51 / 59	57 / 64
serious Total, serious adverse events	21 / 59	0 / 0

Outcome results

Primary

Incidence of Hearing Loss

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