Health Trials

A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss

ConditionChildhood Medulloblastoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age4-21
SponsorChildren's Oncology Group

About this trial

This phase III trial tests two hypotheses in patients with low-risk and average-risk medulloblastoma. Medulloblastoma is a type of cancer that occurs in the back of the brain. The term, risk, refers to the chance of the cancer coming back after treatment. Subjects with low-risk medulloblastoma typically have a lower chance of the cancer coming back than subjects with average-risk medulloblastoma. Although treatment for newly diagnosed average-risk and low-risk medulloblastoma is generally effective at treating the cancer, there are still concerns about the side effects of such treatment. Side effects or unintended health conditions that arise due to treatment include learning difficulties, hearing loss or other issues in performing daily activities. Standard therapy for newly diagnosed average-risk or low-risk medulloblastoma includes surgery, radiation therapy, and chemotherapy (including cisplatin). Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss. Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma patients, the study tests whether a less intense therapy (reduced radiation) can provide the same benefits as the more intense therapy. The less intense therapy may cause fewer side effects. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The overall goals of this study are to see if giving STS along with standard treatment (radiation therapy and chemotherapy) will reduce hearing loss in medulloblastoma patients and to compare the overall outcome of patients with medulloblastoma treated with STS to patients treated without STS on a previous study in order to make sure that survival and recurrence of tumor is not worsened.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

PRE-ENROLLMENT: Patients must be ≥ 4 years and ≤ 21 years of age at the time of enrollment

PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis

Please note: Patients with a pending result of CSF cytology tests are eligible for NCI-2014-02057 (APEC14B1-Central Nervous System [CNS]) and CNS/Medulloblastoma Pre Enrollment Eligibility Screening

PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening and consent for the Molecular Characterization Initiative (MCI)

Disqualifiers

Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible

Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids

Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)

Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential

Trial design

Design model

Single group

Treatments tested in this trial

  • Audiometric Test

    Procedure/Surgery

    Ancillary studies

  • Auditory Brainstem Response

    Procedure/Surgery

    Ancillary studies

  • Biospecimen Collection

    Procedure/Surgery

    Undergo CSF and blood sample collection

  • Cisplatin

    Drug

    Given IV

  • Cyclophosphamide

    Drug

    Given IV

  • Lomustine

    Drug

    Given PO

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Quality-of-Life Assessment

    Other intervention

    Ancillary studies

  • Radiation Therapy

    Radiation

    Undergo radiation therapy

  • Sodium Thiosulfate

    Drug

    Given IV

  • Survey Administration

    Other intervention

    Ancillary studies

  • Vincristine

    Drug

    Given IV

Treatment groups

225 Participants
are divided into 1 treatment group
Group A: Treatment (chemoradiotherapy, maintenance)Experimental treatment 12 interventions

Trial outcomes

Primary outcomes

1

Percentage of patients with >= grade 2 hearing loss

Will estimate the number and percentage of patients with \>= grade 2 hearing loss using the society of pediatric oncology (SIOP) scale (defined as hearing threshold \>20 dB at \>= 4kHz) 4 weeks after the last dose of cisplatin. If hearing loss is observed in both ears, the worse ear will be used for this primary analysis.

Time frame
At 4 weeks after the last dose of cisplatin
2

Event-free survival (EFS)

Will estimate the EFS distribution using Kaplan-Meier (KM) method.

Time frame
From initiation of the protocol treatment to the occurrence of disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 10 years

Secondary outcomes

1

Overall survival (OS)

Will calculate the OS distribution using KM method.

Time frame
Up to 10 years
2

Incidence of ototoxicity-related cisplatin dose modifications in the average-risk cohort

Will be calculated by dividing the total number of ototoxicity-related cisplatin dose modifications by the cumulative dose of cisplatin. Summary statistics including mean, standard deviation (SD), median and range will be used to summarize the data by cohorts.

Time frame
Up to 10 years
3

Incidence of cisplatin-related nephrotoxicity in both the average-risk and low-risk cohorts

The frequency of cisplatin-related nephrotoxicity including Grade 3 and higher creatinine increase, acute kidney injury, and chronic kidney disease will be calculated per patient as raw counts. Summary statistics will be reported including mean, median, standard deviation and range by cohorts.

Time frame
Up to 10 years
4

Full scale intelligence neurocognitive outcomes and trajectories of patients with average-risk medulloblastoma treated with sodium thiosulfate (STS)

A psychologist-administered battery will be used to assess longitudinal trajectories in the estimated full scale intelligence quotient (FSIQ) using the Wechsler Intelligence Scale Vocabulary and Block Design subtest. Box-plots will be drawn for each time point to visually look for change over time. Will estimate pairwise changes in FSIQ between 9 month and 30-month and between 9-month and 60-month measurements. Summary statistics will be provided for each time point and for each pairwise change including mean, standard deviation, median and range. Will compare FSIQ between two time points using parametric or non-parametric one-sample approaches depending on the normality of the data.

Time frame
Up to 5 years

Other outcomes

1

Paired blood and tumor tissue banking or future studies

Will obtain paired blood and tumor tissue to be banked for future biology studies involving comprehensive molecular analysis.

Time frame
Up to 5 years
2

Blood and cerebrospinal fluid banking for future studies

Will bank blood and cerebrospinal fluid for future studies.

Time frame
Up to 5 years
3

Attention, processing speed, memory, and executive function neurocognitive outcomes and trajectories of patients with average-risk medulloblastoma treated with STS

Neurocognitive outcomes (attention, processing speed, and executive function) will also be examined using the approach similar to those used for FSIQ. Will be measured by the Children's Oncology Group Standardized Neuropsychological and Behavioral Batteries.

Time frame
Up to 5 years
4

Hearing related-quality of life (HEAR-QL) of patients with average-risk medulloblastoma treated with STS

Hearing and Audiology Survey will examine parent and patient-perceived hearing loss, hearing aid use, and barriers to hearing aid use through descriptive statistics.

Time frame
Up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Children's Oncology Group

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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