A Phase 3 interventional study of sodium thiosulfate and examination in Brain Tumor, Central Nervous System Tumor and Childhood Germ Cell Tumor, sponsored by Children's Oncology Group. Completed at 76 sites in 3 countries. Open to participants aged 1 Year to 18 Years. Per ClinicalTrials.gov, last updated 2023-11-09.
Sponsored by Children's Oncology Group · Phase 3, Interventional, and Supportive care
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
Secondary
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.
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.
2,440 studies on the registry are indexed under Brain Neoplasms; 540 are open to participants now.
This study's enrollment of 131 is above the median of 40 across 1,831 interventional studies indexed under Brain Neoplasms.
Browse Brain Neoplasms studies →Children's Oncology Group is the lead sponsor of 448 studies on the registry; 36 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Enrolled on hearing assessment clinical trial COG-ACCL05C1
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
No prior platinum-based chemotherapy (cisplatin or carboplatin)
At least 6 months since prior hematopoietic stem cell transplantation.
No concurrent enrollment on another COG clinical trial for treatment of the cancer.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Patients do not receive sodium thiosulfate.
Procedure: examination
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
Patients undergo audiological assessments periodically
Incidence of Hearing Loss
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
Change in Hearing Thresholds For Key Frequencies at 500 hz
Mean change in hearing threshold (post-pre) at 500 hz.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 1000 hz
Mean change in hearing threshold (post-pre) at 1000 hz.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 2000 hz
Mean change in hearing threshold (post-pre) at 2000 hz
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 4000 hz
Mean change in hearing threshold (post-pre) at 4000 hz.
Time frame: 4 weeks after last dose of cisplatin
Change in Hearing Thresholds For Key Frequencies at 8000 hz
Mean change in hearing threshold (post-pre) at 8000 hz.
Time frame: 4 weeks after last dose of cisplatin
Event-Free Survival (EFS)
Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
Time frame: 4 years after enrollment
Overall Survival (OS)
Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
Time frame: 4 Years after enrollment
Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)
Time frame: 4 weeks after the last dose of cisplatin
| Milestone | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Started | 65 | 66 |
| Completed | 45 | 57 |
| Not completed | 20 | 9 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Physician decision | 2 | 2 |
| Withdrew: Withdrawal by subject | 5 | 1 |
| Withdrew: Premature discontinuation cisplatin | 5 | 4 |
| Withdrew: Radiation during protocol | 1 | 0 |
| Withdrew: Ineligibles | 4 | 2 |
Hearing loss defined by comparing hearing sensitivity at follow up evaluation relative to baseline measurements using ASHA criteria.
| Patients | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Incidence of Hearing Loss | 14 | 31 |
Mean change in hearing threshold (post-pre) at 500 hz.
| Decibels | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Change in Hearing Thresholds For Key Frequencies at 500 hz | -1.45 ± 5.80 | -1.11 ± 8.59 |
Mean change in hearing threshold (post-pre) at 1000 hz.
| Decibels | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Change in Hearing Thresholds For Key Frequencies at 1000 hz | -0.676 ± 4.59 | -0.319 ± 8.99 |
Mean change in hearing threshold (post-pre) at 2000 hz
| Decibels | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Change in Hearing Thresholds For Key Frequencies at 2000 hz | -1.18 ± 4.85 | 0.638 ± 12.7 |
Mean change in hearing threshold (post-pre) at 4000 hz.
| Decibels | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Change in Hearing Thresholds For Key Frequencies at 4000 hz | 1.05 ± 7.09 | 9.58 ± 20.5 |
Mean change in hearing threshold (post-pre) at 8000 hz.
| Decibels | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Change in Hearing Thresholds For Key Frequencies at 8000 hz | 9.73 ± 17.3 | 17.0 ± 24.7 |
Proportion of patients event free at 4 years following enrollment. See EFS outcome measure description.
| Percentage probability | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Event-Free Survival (EFS) | 53.7 (39.8 to 65.8) | 61.4 (48.0 to 72.3) |
Proportion of patients alive free at 4 years following enrollment. See OS outcome measure description.
| Percentage probability | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Overall Survival (OS) | 69.6 (55.6 to 79.9) | 82.0 (68.4 to 90.1) |
No measurements were reported for this outcome.
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| STS Arm (Sodium Thiosulfate Treatment) | — | 21/59 (35.6%) | 51/59 (86.4%) |
| Observation Arm | — | — | 57/64 (89.1%) |
| Event | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 12/59 | — |
| Neutrophil count decreasedInvestigations | 10/59 | — |
| Platelet count decreasedInvestigations | 8/59 | — |
| White blood cell decreasedInvestigations | 8/59 | — |
| AnemiaBlood and lymphatic system disorders | 7/59 | — |
| Mucositis oralGastrointestinal disorders | 5/59 | — |
| Lymphocyte count decreasedInvestigations | 4/59 | — |
| Alanine aminotransferase increasedInvestigations | 3/59 | — |
| Infections and infestations - Other, specifyInfections and infestations | 3/59 | — |
| AnorexiaMetabolism and nutrition disorders | 2/59 | — |
| Event | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm |
|---|---|---|
| Neutrophil count decreasedInvestigations | 39/59 | 51/64 |
| White blood cell decreasedInvestigations | 30/59 | 42/64 |
| Platelet count decreasedInvestigations | 30/59 | 39/64 |
| AnemiaBlood and lymphatic system disorders | 23/59 | 36/64 |
| Febrile neutropeniaBlood and lymphatic system disorders | 2/59 | 19/64 |
| HypokalemiaMetabolism and nutrition disorders | 15/59 | 13/64 |
| HypophosphatemiaMetabolism and nutrition disorders | 12/59 | 7/64 |
| Alanine aminotransferase increasedInvestigations | 7/59 | 9/64 |
| Infections and infestations - Other, specifyInfections and infestations | 3/59 | 9/64 |
| Lymphocyte count decreasedInvestigations | 2/59 | 9/64 |
| Age, Categorical(Participants) | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm | Total |
|---|---|---|---|
| <=18 years | 65 | 66 | 131 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(Years) | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm | Total |
|---|---|---|---|
| Mean | 8.97 ± 5.93 | 8.39 ± 5.88 | 8.68 ± 5.89 |
| Sex: Female, Male(Participants) | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm | Total |
|---|---|---|---|
| Female | 27 | 24 | 51 |
| Male | 38 | 42 | 80 |
| Ethnicity (NIH/OMB)(Participants) | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm | Total |
|---|---|---|---|
| Hispanic or Latino | 19 | 15 | 34 |
| Not Hispanic or Latino | 44 | 48 | 92 |
| Unknown or Not Reported | 2 | 3 | 5 |
| Race (NIH/OMB)(Participants) | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 1 | 2 | 3 |
| Native Hawaiian or Other Pacific Islander | 1 | 1 | 2 |
| Black or African American | 7 | 10 | 17 |
| White | 44 | 41 | 85 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 11 | 12 | 23 |
| Region of Enrollment(participants) | STS Arm (Sodium Thiosulfate Treatment) | Observation Arm | Total |
|---|---|---|---|
| Canada | 8 | 4 | 12 |
| United States | 56 | 62 | 118 |
Ran from Jun 2008 to primary completion in Apr 2015, 81 months.
Results were first posted in Jun 2017, 2 years 1 month after primary completion. A results delay was requested in Apr 2014.
Of 56 phase 3 interventional studies under Brain Neoplasms, half reached primary completion within 81 months of starting (the median), counting those still running; a quarter within 48 and three quarters within 269. This study's 81 months is close to that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sodium thiosulfate