Low-Dose Radiation Therapy and Combination Chemotherapy Following Surgery in Treating Children With Newly Diagnosed Primitive Neuroectodermal Tumor or Medulloblastoma

OBJECTIVES:

- Reduce the late cognitive, auditory, and endocrinologic effects in children with newly
diagnosed standard-risk posterior fossa primitive neuroectodermal tumor or
medulloblastoma by reducing the adjuvant craniospinal radiotherapy dose by 25%, but
maintaining a therapeutic efficacy (86% 3-year relapse-free survival) of current
standard therapy by using maintenance chemotherapy comprising lomustine, cisplatin, and
vincristine alternated with cyclophosphamide and etoposide.

- Evaluate the acute and subacute toxicity of this regimen in these patients.

- Evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of
cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multicenter study.

- Adjuvant induction chemoradiotherapy: Beginning within 28 days after prior resection,
patients undergo radiotherapy to the craniospinal axis 5 days a week for 2 weeks and
then conformal radiotherapy to the tumor bed 5 days a week for 4 weeks. Beginning 1
week after the initiation of radiotherapy, patients receive vincristine IV weekly for 6
weeks.

- Maintenance chemotherapy: Beginning 4 weeks after the completion of induction
chemoradiotherapy, patients receive two 6-week courses of regimen A as outlined below
alternated with one 6-week course of regimen B as outlined below for a total of 9
courses (6 courses of regimen A and 3 courses of regimen B).

- Regimen A: Patients receive oral lomustine and cisplatin IV over 8 hours on day 0
and vincristine IV on days 0, 7, and 14.

- Regimen B: Patients receive cyclophosphamide IV on days 0 and 1 and etoposide IV
on days 0 and 1 and then orally on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.

Inclusion Criteria:

1. Histologically confirmed posterior fossa primitive neuroectodermal tumor or
medulloblastoma

2. Standard-risk disease

3. No residual tumor greater than 1.5 cm^2 after resection by postoperative MRI

- No tumor in the spinal or cerebral subarachnoid space by MRI

- No tumor in the subarachnoid space by Cerebrospinal fluid (CSF)

- No failure to perform staging studies (spine MRI and CSF cytology)
preoperatively or postoperatively

4. Must begin radiotherapy on study within 28 days after surgery

Exclusion Criteria:

1. Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not
allowed.

2. Pregnant females will not be eligible

3. Patients must begin radiotherapy on protocol within 28 days of completion of surgery.
Exceptions need to be approved by the Principal Investigator.

4. Patients with the following will not be eligible:

- > 1.5cm3 residual tumor following resection as indicated by post-operative MRI.

- tumor in spinal or cerebral subarachnoid space either by MRI of brain and spine

- tumor in subarachnoid space by CSF cytology

- failure to perform staging studies (spine MRI, CSF cytology) either pre- or
post- operatively