Sodium Thiosulfate for Reduction of Cisplatin-Induced Ototoxicity in Children With Average-Risk Medulloblastoma and Reduced Therapy in Children With Medulloblastoma With Low-Risk Features

• Status: Not yet recruiting
• Trial end date: 2027-12-20
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this study is to reduce cisplatin-induced ototoxicity with sodium thiosulfate (STS) in children (ages 4-21 years) with newly-diagnosed average-risk and low-risk medulloblastoma. This trial will also evaluate the tumor protection potential of STS in a disease-focused setting by monitoring survival against a carefully selected historical control cohort treated identically using the ACNS0331 backbone.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Lomustine; Sodium thiosulfate; Vincristine

Criteria

Inclusion Criteria:

• Patients must be newly diagnosed and have eligibility confirmed by rapid central pathology and molecular screening reviews performed on APEC14B1 and via the Molecular Characterization Initiative

Average-Risk Cohort:

Clinico-pathologic criteria:

• M0 disease

• No diffuse anaplastic histology AND

Molecular criteria:

• SHH, p53wt, GLI2 normal, MYCN normal, no chromosome 14q loss

• Group 3, MYC normal, no isochromosome 17q

• Group 4, no chromosome 11 loss

Low-Risk Features Cohort:

Clinico-pathologic criteria:

• M0 disease

• No diffuse anaplastic histology AND

Molecular criteria:

• Group 4, chromosome 11 loss Patients must have negative lumbar CSF cytology

• Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between Day 14 and Day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively.

• Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1. Patients must have ≤ 1.5 cm2 cross-sectional area of residual tumor Whole brain MRI with and without gadoliniumand spine MRI with gadolinium must be performed.

• Patients must weigh > 10 kg

• Patients must be enrolled, and protocol therapy must be projected to begin, no later than 31 days after definitive diagnostic surgery (Day 0)

• Adequate bone marrow function defined as:

• Peripheral absolute neutrophil count (ANC) ≥ 1000/µL

• Platelet count ≥ 100,000/µL (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

• Adequate renal function defined as:

• A serum creatinine based on age/gender OR - a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2 OR - a GFR ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).

• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.

• Adequate liver function defined as:

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and

• SGPT (ALT) ≤ 135 U/L*

• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

• Central nervous system function defined as:

• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.

• Patients must not be in status epilepticus, a coma or assisted ventilation at the time of study enrollment.

• Auditory function defined as:

Patients must have normal hearing (defined as SIOP Grade 0) in at least one ear confirmed by rapid central audiology review performed on APEC14B1 prior to enrollment

Exclusion Criteria:

• 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.

• Prior to therapy 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 (eg, amifostine, Nacetylcysteine,MESNA, and captopril).

• Pregnancy and Breastfeeding

• 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.

• Lactating females who plan to breastfeed their infants.

• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

• All patients and/or their parents or legal guardians must sign a written informed consent.

• All institutional, FDA, and NCI requirements for human studies must be met.