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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Purpose
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 compared with no additional treatment in preventing hearing loss in young patients receiving cisplatin for newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor Liver Cancer Neuroblastoma Ototoxicity Ovarian Cancer Sarcoma |
Drug: sodium thiosulfate Procedure: examination |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Masking: Open Label Primary Purpose: Supportive Care |
| Official Title: | A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children |
- Incidence of hearing loss [ Designated as safety issue: No ]
- Mean change in hearing thresholds for key frequencies [ Designated as safety issue: No ]
- Incidences of cisplatin-related grade 3 and 4 nephrotoxicity and grade 3 and 4 cytopenia [ Designated as safety issue: Yes ]
- Event-free-survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Association of two key gene mutations (TPMT and COMT) with the development of cisplatin-induced hearing loss [ Designated as safety issue: No ]
| Estimated Enrollment: | 135 |
| Study Start Date: | June 2008 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: sodium thiosulfate
Given IV
Procedure: examination
Patients undergo audiological assessments periodically
|
|
No Intervention: Arm II (observation)
Patients do not receive sodium thiosulfate.
|
Procedure: examination
Patients undergo audiological assessments periodically
|
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.
Eligibility| Ages Eligible for Study: | 1 Year to 18 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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., Headstart) allowed
No concurrent cranial irradiation during the chemotherapy regimen (i.e., prior to the administration of the final dose of cisplatin)
- 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
Contacts and Locations
Show 77 Study Locations| Study Chair: | David R. Freyer, DO, MS | Children's Hospital Los Angeles |
More Information
Additional Information:
No publications provided
| Responsible Party: | Brad H. Pollock, Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00716976 History of Changes |
| Other Study ID Numbers: | CDR0000588655, COG-ACCL0431 |
| Study First Received: | July 15, 2008 |
| Last Updated: | July 12, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
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 |
Additional relevant MeSH terms:
|
Liver Neoplasms Medulloblastoma Nervous System Neoplasms Neuroblastoma Osteosarcoma Ovarian Neoplasms Central Nervous System Neoplasms Neoplasms, Germ Cell and Embryonal Hepatoblastoma Sarcoma Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Liver Diseases |
Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms by Histologic Type Neuroectodermal Tumors, Primitive Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Nervous System Diseases Neuroectodermal Tumors, Primitive, Peripheral Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Endocrine Gland Neoplasms Ovarian Diseases Adnexal Diseases |
ClinicalTrials.gov processed this record on May 16, 2013