Trial Information

A PHASE III PROSPECTIVE RANDOMIZED STUDY OF CRANIOSPINAL RADIOTHERAPY FOLLOWED BY ONE OF TWO ADJUVANT CHEMOTHERAPY REGIMENS (CCNU, CDDP, VCR OR CPM, CDDP, VCR) IN CHILDREN WITH NEWLY-DIAGNOSED AVERAGE-RISK MEDULLOBLASTOMA

OBJECTIVES: I. Assess whether a cyclophosphamide-containing combination chemotherapy regimen
increases progression-free survival compared to a lomustine-containing regimen in children
with newly diagnosed, average-risk medulloblastoma. II. Determine progression-free and
overall survival of children treated with craniospinal radiotherapy and local boost
radiotherapy for a total dose of 5580 cGy followed by adjuvant
lomustine/cisplatin/vincristine vs. cyclophosphamide/cisplatin/vincristine. III. Determine
the long-term neurocognitive, endocrinologic, and cardiopulmonary sequelae associated with
craniospinal radiotherapy, local boost radiotherapy, and adjuvant chemotherapy in these
children, and determine whether replacement of lomustine with cyclophosphamide alters the
incidence and degree of sequelae. IV. Determine whether cellular and biologic parameters,
including tumor molecular genetic analysis, DNA ploidy, mitotic activity markers, and
immunohistochemical analysis, are correlated with progression-free survival, overall
survival, and patterns of disease relapse in these patients. V. Evaluate the utility of
routine magnetic resonance imaging surveillance studies of the head and spine in detecting
subclinical recurrent disease.

OUTLINE: This is a randomized study. Patients are stratified by participating institution.
Following surgery, patients are randomized to one of two groups. The first group receives
craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week
after initiation of radiotherapy, patients receive vincristine weekly for 8 doses. Beginning
6 weeks after the completion of radiotherapy, patients receive adjuvant
lomustine/vincristine/cisplatin every 6 weeks for a total of 8 courses. The second group
receives craniospinal irradiation plus vincristine as above, followed by adjuvant
cyclophosphamide/vincristine/cisplatin every 6 weeks for a total of 8 courses. Patients are
followed every 3 months for 1 year, every 6 months for 2 years, then annually.

PROJECTED ACCRUAL: It is anticipated that 240-300 patients will be entered over 4 years.