Reduced Therapy for Newly Diagnosed Medulloblastoma Patients

Summary

This study focuses on individuals who have been diagnosed with a cancer called medulloblastoma (MB), which is a type of childhood brain tumor that grows in the very back of the brain. Participants in the study are at least 3 years old and have “average-risk” MB, meaning that the tumor has been completely removed or almost completely removed by surgery, and the cancer has not spread to other parts of the brain or spinal cord. They also have classic MB of the WNT-subgroup; these patients have been shown to have better survival than other types of MB. The purpose of the study is to determine whether a reduced dose of radiation to the whole brain and spine and less chemotherapy can be given to children and young adults with WNT-subgroup MB without increasing the risk of the tumor returning. The combination of a reduction in radiation therapy and chemotherapy is experimental. Researchers also aim to better understand the biology of WNT-subgroup MB, as well as closely examine the brain function as it relates to thinking and learning in children with WNT-subgroup MB after they receive treatment on this study.

Inclusion Criteria

Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment
Patients must be newly diagnosed and have:

Inclusion Criteria:

Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment
Patients must be newly diagnosed and have:
Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1 and via the Molecular Characterization Initiative:
Classical histologic type (non LC/A) WNT medulloblastoma
Positive nuclear beta-catenin by immunohistochemistry (IHC)
Positive for CTNNB1 mutation
Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)
Patient must have negative lumbar cerebrospinal fluid (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 on APEC14B1; patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with gadolinium must be performed
Patients must be enrolled, and protocol therapy must be projected to begin, no later than 36 days after definitive diagnostic surgery (day 0)
Peripheral absolute neutrophil count (ANC) >= 1000/uL
Platelet count >= 100,000/uL (transfusion independent)
Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and females)
6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)
10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)
13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)
>= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 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 on assisted ventilation at the time of study enrollment
Patients must have receptive and expressive language skills in English, French, or Spanish to complete the QoL and neurocognitive assessments; if a patient meets these criteria but the parent/guardian speaks a language other than English, French, or Spanish, the patient may still be enrolled and tested, and the parent-report measures should be omitted
All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
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 (brain and spine) 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
Pregnancy and Breast Feeding
Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
Patients with a history of moderate to profound intellectual disability (i.e., intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE: Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a specific learning disability (e.g., dyslexia) are eligible for this study. Children with posterior fossa syndrome (also known as cerebellar mutism) are eligible for this study