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

Inclusion Criteria:

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

• PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma byinstitutional diagnosis

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

• PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signedinformed consent for APEC14B1 Part A - Eligibility Screening and consent for theMolecular Characterization Initiative (MCI)

• PRE-ENROLLMENT: The required specimens are projected to be submitted underAPEC14B1-CNS as soon as possible, preferably within 5 days of definitive surgery

• PRE-ENROLLMENT: All patients must have rapid central pathology review underAPEC14B1-CNS prior to study enrollment on ACNS2031 step 1 in order to avoiddiscordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031.

• Note: Patients with a pending result of CSF cytology tests are eligible for therapid central pathology screening review. Confirmation of CSF negativity isneeded for enrollment on the ACNS2031 protocol

• PRE-ENROLLMENT: All patients must have rapid central molecular screening reviewunder APEC14B1-CNS prior to study enrollment on ACNS2031 step 1, in order to avoiddiscordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031

• PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapidcentral imaging screening review under APEC14B1 prior to study enrollment onACNS2031 step 1

• Note: Patients must not have metastatic disease on cranial or spinal MRI.Patients with > 1.5 cm^2 residual tumor after initial surgical resection mayundergo a second surgical resection prior to subsequent therapy to render themeligible for this study. The day of the second resection to remove residualtumor will be regarded as the day of definitive surgery (Day 0) and must bewithin a month (31 days) of the initial resection

• PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapidcentral audiology review under APEC14B1-CNS prior to study enrollment on ACNS2031step 1

• Patients must be >= 4 years and =< 21 years of age at the time of enrollment

• Patients must be newly diagnosed and have eligibility confirmed by rapid centralpathology and molecular screening reviews performed on APEC14B1 and via theMolecular 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 postoperatively to avoid false positive CSF. Ideally, CSF should be obtainedbetween day 14 and day 21 to allow for final staging status before enrollmentonto the study. Patients with positive CSF cytology obtained 0 to 14 days aftersurgery should have cytology repeated to determine eligibility and final CSFstatus. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSFcytology from lumbar puncture obtained prior to surgery do not need cytologyrepeated post-operatively

• Patients must have eligibility confirmed by Rapid Central Imaging Review performedon APEC14B1. Patients must have =< 1.5 cm^2 cross-sectional area of residual tumor.Whole brain MRI with and without gadolinium and spine MRI with gadolinium must beperformed

• Patients must weigh > 10 kg

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

• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior toenrollment)

• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior toenrollment)

• Hemoglobin >= 8.0 g/dL (may receive red blood cell count [RBC] transfusions) (within 7 days prior to enrollment)

• A serum creatinine (within 7 days prior to enrollment) based on age/sex as follows:

• 4 to < 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female)

• 6 to < 10 years (age); 1 mg/dL (male) 1 mg/dL (female)

• 10 to < 13 years (age); 1.2 mg/dL (male) 1.2 mg/dL (female)

• 13 to < 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female)

• >= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female) OR a 24 hour urineCreatinine clearance >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment)OR a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 daysprior to enrollment). GFR must be performed using direct measurement with anuclear 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 estimatesare not acceptable for determining eligibility

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior toenrollment)

• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135U/L (within 7 days prior to enrollment)

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

• Central nervous system function defined as:

• Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled

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

• Auditory function defined as:

• Patients must have normal hearing (defined as International Society ofPediatric Oncology [SIOP] grade 0) in at least one ear confirmed by rapidcentral audiology review performed on APEC14B1 prior to enrollment

• All patients and/or their parents or legal guardians must sign a written informedconsent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology arenot eligible. Patients who are unable to undergo a lumbar puncture for assessment ofCSF 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, orother thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)

• Pregnancy and Breastfeeding:

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

• Lactating females who plan to breastfeed their infants

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