Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma

PRIMARY OBJECTIVES:

I. Estimate of the progression free survival (PFS) distribution for patients 0-<4 years of
age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with
extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of
intraventricular methotrexate).

OTHER PRE-SPECIFIED OBJECTIVES:

I. Evaluate the feasibility of a rapid central pathology screening review for treatment
allocation according to histology and assess agreement between institutional and central
pathology review diagnoses as well as among central pathology review diagnoses.

II. Prospectively evaluate the molecular profile of nodular desmoplastic (ND)/medulloblastoma
with extensive nodularity (MBEN) medulloblastoma in young children.

III. Monitor and describe the neurocognitive and adaptive functioning of young children with
ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.

OUTLINE:

INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute or
infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3;
methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days
43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3
courses in the absence of disease progression or unacceptable toxicity.

CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via
minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120
minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every
42 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 16, 20, 24, 36,
48, 60, and 72 months.

Inclusion Criteria:

- Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular
desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN)
from rapid central pathology screening review; please note: patients with Gorlin
syndrome are eligible

- Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must
be obtained unless medically contraindicated); CSF cytology for staging should be
performed preferably 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; Note: patients with positive CSF
cytology obtained prior to 14 days after surgery may have cytology repeated to
determine eligibility and final CSF status

- Patients must have:

- Pre-operative cranial magnetic resonance imaging (MRI) (recommended with
gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)

- Post-operative cranial MRI with and without gadolinium within 72 hours of surgery

- Spinal MRI pre-op with and without gadolinium or post-op with and without
gadolinium preferably within 72 hours of surgery

- Patients must be enrolled on study within 31 days of definitive surgical resection at
which time tissue is acquired to determine a diagnosis; patients must be enrolled
before treatment begins; the date protocol therapy is projected to start must be no
later than five (5) calendar days after the date of study enrollment; patients who are
started on protocol therapy on a Phase II study prior to study enrollment will be
considered ineligible

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =< 16 years of age

- Patients must have a life expectancy of >= 8 weeks

- Patients who are receiving dexamethasone must be on a stable dose for at least 1 week
prior to study entry

- Peripheral absolute neutrophil count (ANC) >= 1000/uL

- Platelet count >= 100,000/uL (transfusion independent)

- Hemoglobin >= 10.0 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:

- 1 month to < 6 months: 0.4 mg/dL

- 6 months to < 1 year: 0.5 mg/dL

- 1 to < 2 years: 0.6 mg/dL

- 2 to < 6 years: 0.8 mg/dL

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age

- 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, coma or assisted ventilation prior to study
enrollment

Exclusion Criteria:

- Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar
CSF cytology are not eligible

- Patients must not have received any prior tumor-directed therapy other than surgical
intervention and corticosteroids