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

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ClinicalTrials.gov Identifier: NCT00716976
Recruitment Status : Completed
First Posted : July 16, 2008
Results First Posted : February 26, 2014
Last Update Posted : September 20, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Conditions Brain Tumor
Central Nervous System Tumor
Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Liver Cancer
Neuroblastoma
Ototoxicity
Ovarian Cancer
Sarcoma
Interventions Drug: sodium thiosulfate
Procedure: examination
Enrollment 131
Recruitment Details  
Pre-assignment Details  
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description Sodium thiosulfate treatment. No sodium thiosulfate treatment.
Period Title: Overall Study
Started 65 66
Completed 45 57
Not Completed 20 9
Reason Not Completed
Adverse Event             2             0
Death             1             0
Physician Decision             2             2
Withdrawal by Subject             5             1
Premature discontinuation cisplatin             5             4
Radiation during protocol             1             0
Ineligibles             4             2
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm Total
Hide Arm/Group Description Sodium thiosulfate treatment. No sodium thiosulfate treatment. Total of all reporting groups
Overall Number of Baseline Participants 65 66 131
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 66 participants 131 participants
<=18 years
65
 100.0%
66
 100.0%
131
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 66 participants 131 participants
8.97  (5.93) 8.39  (5.88) 8.68  (5.89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 66 participants 131 participants
Female
27
  41.5%
24
  36.4%
51
  38.9%
Male
38
  58.5%
42
  63.6%
80
  61.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 66 participants 131 participants
Hispanic or Latino
19
  29.2%
15
  22.7%
34
  26.0%
Not Hispanic or Latino
44
  67.7%
48
  72.7%
92
  70.2%
Unknown or Not Reported
2
   3.1%
3
   4.5%
5
   3.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 66 participants 131 participants
American Indian or Alaska Native
1
   1.5%
0
   0.0%
1
   0.8%
Asian
1
   1.5%
2
   3.0%
3
   2.3%
Native Hawaiian or Other Pacific Islander
1
   1.5%
1
   1.5%
2
   1.5%
Black or African American
7
  10.8%
10
  15.2%
17
  13.0%
White
44
  67.7%
41
  62.1%
85
  64.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
11
  16.9%
12
  18.2%
23
  17.6%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 65 participants 66 participants 131 participants
Canada 8 4 12
United States 56 62 118
[1]
Measure Description: 1 patient of unknown origin in STS arm
1.Primary Outcome
Title Incidence of Hearing Loss
Hide Description Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
Time Frame 4 weeks after last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 49 55
Measure Type: Number
Unit of Measure: Patients
14 31
2.Secondary Outcome
Title Change in Hearing Thresholds For Key Frequencies at 500 hz
Hide Description Mean change in hearing threshold (post-pre) at 500 hz.
Time Frame 4 weeks after last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 38 45
Mean (Standard Deviation)
Unit of Measure: Decibels
-1.45  (5.80) -1.11  (8.59)
3.Secondary Outcome
Title Change in Hearing Thresholds For Key Frequencies at 1000 hz
Hide Description Mean change in hearing threshold (post-pre) at 1000 hz.
Time Frame 4 weeks after last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 37 47
Mean (Standard Deviation)
Unit of Measure: Decibels
-0.676  (4.59) -0.319  (8.99)
4.Secondary Outcome
Title Change in Hearing Thresholds For Key Frequencies at 2000 hz
Hide Description Mean change in hearing threshold (post-pre) at 2000 hz
Time Frame 4 weeks after last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 38 47
Mean (Standard Deviation)
Unit of Measure: Decibels
-1.18  (4.85) 0.638  (12.7)
5.Secondary Outcome
Title Change in Hearing Thresholds For Key Frequencies at 4000 hz
Hide Description Mean change in hearing threshold (post-pre) at 4000 hz.
Time Frame 4 weeks after last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 38 47
Mean (Standard Deviation)
Unit of Measure: Decibels
1.05  (7.09) 9.58  (20.5)
6.Secondary Outcome
Title Change in Hearing Thresholds For Key Frequencies at 8000 hz
Hide Description Mean change in hearing threshold (post-pre) at 8000 hz.
Time Frame 4 weeks after last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 38 42
Mean (Standard Deviation)
Unit of Measure: Decibels
9.73  (17.3) 17.0  (24.7)
7.Secondary Outcome
Title Event-Free Survival (EFS)
Hide Description Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Time Frame 4 years after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
61 eligible patients were enrolled on the STS arm; 64 eligible patients were enrolled on the observation arm.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 61 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage probability
53.7
(39.8 to 65.8)
61.4
(48.0 to 72.3)
8.Secondary Outcome
Title Overall Survival (OS)
Hide Description Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Time Frame 4 Years after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
61 eligible patients were enrolled on the STS arm; 64 eligible patients were enrolled on the observation arm.
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description:
Sodium thiosulfate treatment.
No sodium thiosulfate treatment.
Overall Number of Participants Analyzed 61 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage probability
69.6
(55.6 to 79.9)
82.0
(68.4 to 90.1)
9.Secondary Outcome
Title Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
Hide Description [Not Specified]
Time Frame 4 weeks after the last dose of cisplatin
Hide Outcome Measure Data
Hide Analysis Population Description
Data was and never will be collected
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm (No Sodium Thiosulfate Treatment)
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description 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.
 
Arm/Group Title STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   21/59 (35.59%)   0/0 
Blood and lymphatic system disorders     
Anemia  7/59 (11.86%)  0/0 
Febrile neutropenia  12/59 (20.34%)  0/0 
Cardiac disorders     
Cardiac arrest  1/59 (1.69%)  0/0 
Eye disorders     
Conjunctivitis  1/59 (1.69%)  0/0 
Gastrointestinal disorders     
Abdominal pain  1/59 (1.69%)  0/0 
Colitis  1/59 (1.69%)  0/0 
Mucositis oral  5/59 (8.47%)  0/0 
Nausea  2/59 (3.39%)  0/0 
Oral pain  1/59 (1.69%)  0/0 
Rectal pain  1/59 (1.69%)  0/0 
Typhlitis  1/59 (1.69%)  0/0 
Vomiting  1/59 (1.69%)  0/0 
Immune system disorders     
Anaphylaxis  1/59 (1.69%)  0/0 
Infections and infestations     
Abdominal infection  1/59 (1.69%)  0/0 
Infections and infestations - Other, specify  3/59 (5.08%)  0/0 
Urinary tract infection  1/59 (1.69%)  0/0 
Investigations     
Alanine aminotransferase increased  3/59 (5.08%)  0/0 
Aspartate aminotransferase increased  1/59 (1.69%)  0/0 
Lymphocyte count decreased  4/59 (6.78%)  0/0 
Neutrophil count decreased  10/59 (16.95%)  0/0 
Platelet count decreased  8/59 (13.56%)  0/0 
Weight loss  1/59 (1.69%)  0/0 
White blood cell decreased  8/59 (13.56%)  0/0 
Metabolism and nutrition disorders     
Acidosis  1/59 (1.69%)  0/0 
Anorexia  2/59 (3.39%)  0/0 
Dehydration  2/59 (3.39%)  0/0 
Hypocalcemia  1/59 (1.69%)  0/0 
Hypoglycemia  1/59 (1.69%)  0/0 
Hypokalemia  1/59 (1.69%)  0/0 
Hypomagnesemia  1/59 (1.69%)  0/0 
Hyponatremia  1/59 (1.69%)  0/0 
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorder - Other, specify  1/59 (1.69%)  0/0 
Nervous system disorders     
Depressed level of consciousness  1/59 (1.69%)  0/0 
Extrapyramidal disorder  1/59 (1.69%)  0/0 
Reversible posterior leukoencephalopathy syndrome  1/59 (1.69%)  0/0 
Syncope  2/59 (3.39%)  0/0 
Psychiatric disorders     
Anxiety  1/59 (1.69%)  0/0 
Respiratory, thoracic and mediastinal disorders     
Pharyngeal stenosis  1/59 (1.69%)  0/0 
Vascular disorders     
Hypotension  1/59 (1.69%)  0/0 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
STS Arm (Sodium Thiosulfate Treatment) Observation Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   51/59 (86.44%)   57/64 (89.06%) 
Blood and lymphatic system disorders     
Anemia  23/59 (38.98%)  36/64 (56.25%) 
Febrile neutropenia  2/59 (3.39%)  19/64 (29.69%) 
Ear and labyrinth disorders     
Hearing impaired  0/59 (0.00%)  1/64 (1.56%) 
Middle ear inflammation  0/59 (0.00%)  1/64 (1.56%) 
Gastrointestinal disorders     
Colitis  0/59 (0.00%)  1/64 (1.56%) 
Constipation  0/59 (0.00%)  1/64 (1.56%) 
Esophageal pain  0/59 (0.00%)  1/64 (1.56%) 
Esophageal ulcer  1/59 (1.69%)  0/64 (0.00%) 
Esophagitis  0/59 (0.00%)  1/64 (1.56%) 
Mucositis oral  3/59 (5.08%)  4/64 (6.25%) 
Nausea  3/59 (5.08%)  3/64 (4.69%) 
Vomiting  3/59 (5.08%)  3/64 (4.69%) 
General disorders     
Chills  2/59 (3.39%)  0/64 (0.00%) 
Infusion related reaction  0/59 (0.00%)  2/64 (3.13%) 
Pain  1/59 (1.69%)  0/64 (0.00%) 
Immune system disorders     
Allergic reaction  5/59 (8.47%)  3/64 (4.69%) 
Infections and infestations     
Abdominal infection  0/59 (0.00%)  1/64 (1.56%) 
Bone infection  1/59 (1.69%)  0/64 (0.00%) 
Catheter related infection  0/59 (0.00%)  3/64 (4.69%) 
Device related infection  0/59 (0.00%)  1/64 (1.56%) 
Enterocolitis infectious  0/59 (0.00%)  1/64 (1.56%) 
Esophageal infection  0/59 (0.00%)  1/64 (1.56%) 
Infections and infestations - Other, specify  3/59 (5.08%)  9/64 (14.06%) 
Otitis media  1/59 (1.69%)  0/64 (0.00%) 
Paronychia  0/59 (0.00%)  1/64 (1.56%) 
Penile infection  0/59 (0.00%)  1/64 (1.56%) 
Pharyngitis  1/59 (1.69%)  0/64 (0.00%) 
Sepsis  0/59 (0.00%)  2/64 (3.13%) 
Sinusitis  1/59 (1.69%)  1/64 (1.56%) 
Skin infection  1/59 (1.69%)  2/64 (3.13%) 
Upper respiratory infection  0/59 (0.00%)  1/64 (1.56%) 
Urinary tract infection  1/59 (1.69%)  1/64 (1.56%) 
Wound infection  0/59 (0.00%)  1/64 (1.56%) 
Investigations     
Alanine aminotransferase increased  7/59 (11.86%)  9/64 (14.06%) 
Aspartate aminotransferase increased  4/59 (6.78%)  5/64 (7.81%) 
Blood bilirubin increased  1/59 (1.69%)  0/64 (0.00%) 
GGT increased  3/59 (5.08%)  1/64 (1.56%) 
Lymphocyte count decreased  2/59 (3.39%)  9/64 (14.06%) 
Neutrophil count decreased  39/59 (66.10%)  51/64 (79.69%) 
Platelet count decreased  30/59 (50.85%)  39/64 (60.94%) 
Weight loss  1/59 (1.69%)  0/64 (0.00%) 
White blood cell decreased  30/59 (50.85%)  42/64 (65.63%) 
Metabolism and nutrition disorders     
Acidosis  1/59 (1.69%)  1/64 (1.56%) 
Anorexia  2/59 (3.39%)  4/64 (6.25%) 
Dehydration  1/59 (1.69%)  3/64 (4.69%) 
Hyperglycemia  1/59 (1.69%)  1/64 (1.56%) 
Hyperkalemia  1/59 (1.69%)  0/64 (0.00%) 
Hypermagnesemia  1/59 (1.69%)  3/64 (4.69%) 
Hypernatremia  7/59 (11.86%)  4/64 (6.25%) 
Hypoalbuminemia  1/59 (1.69%)  0/64 (0.00%) 
Hypocalcemia  4/59 (6.78%)  2/64 (3.13%) 
Hypokalemia  15/59 (25.42%)  13/64 (20.31%) 
Hypomagnesemia  2/59 (3.39%)  2/64 (3.13%) 
Hyponatremia  7/59 (11.86%)  4/64 (6.25%) 
Hypophosphatemia  12/59 (20.34%)  7/64 (10.94%) 
Musculoskeletal and connective tissue disorders     
Bone pain  0/59 (0.00%)  1/64 (1.56%) 
Joint range of motion decreased  1/59 (1.69%)  0/64 (0.00%) 
Pain in extremity  0/59 (0.00%)  1/64 (1.56%) 
Nervous system disorders     
Leukoencephalopathy  1/59 (1.69%)  0/64 (0.00%) 
Peripheral motor neuropathy  1/59 (1.69%)  1/64 (1.56%) 
Peripheral sensory neuropathy  1/59 (1.69%)  0/64 (0.00%) 
Psychiatric disorders     
Anxiety  1/59 (1.69%)  0/64 (0.00%) 
Confusion  1/59 (1.69%)  0/64 (0.00%) 
Reproductive system and breast disorders     
Perineal pain  1/59 (1.69%)  0/64 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1/59 (1.69%)  0/64 (0.00%) 
Hypoxia  1/59 (1.69%)  0/64 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin ulceration  1/59 (1.69%)  0/64 (0.00%) 
Vascular disorders     
Hypertension  1/59 (1.69%)  0/64 (0.00%) 
Hypotension  1/59 (1.69%)  1/64 (1.56%) 
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).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00716976     History of Changes
Other Study ID Numbers: ACCL0431
COG-ACCL0431 ( Other Identifier: Children's Oncology Group )
CDR0000588655 ( Other Identifier: Clinical Trials.gov )
First Submitted: July 15, 2008
First Posted: July 16, 2008
Results First Submitted: December 9, 2016
Results First Posted: February 26, 2014
Last Update Posted: September 20, 2018