Trial Information

Multicenter Therapy Optimizing Study for Treatment of Children and Adolescents With Intracranial Medulloblastoma / PNET and Ependymoma

OBJECTIVES:

- Compare prognosis, using adapted risk stratification and quality control of diagnostic
assessments and therapy, in pediatric patients with intracranial medulloblastoma,
supratentorial primitive neuroectodermal tumor (PNET), or ependymoma treated with
intensified chemotherapy and radiotherapy.

- Determine the effect of omission of radiotherapy, in terms of long-term sequelae, in
young children with medulloblastoma and by hyperfractionation and reduction of
radiotherapy in older children with medulloblastoma.

- Compare hyperfractionated radiotherapy with reduced-dose radiotherapy in older children
with stage M0 medulloblastoma.

OUTLINE: This is a multi-protocol study. Patients are enrolled on 1 of 6 treatment protocols
according to diagnosis and age at diagnosis.

- Protocol HIT-2000-AB4 (≥ 4 years old at diagnosis with nonmetastatic
medulloblastoma)(phase III randomized controlled multicenter study): Patients are
randomized to undergo hyperfractionated radiotherapy or conventional reduced-dose
radiotherapy, followed by vincristine, lomustine, and cisplatin.

- Protocol HIT-2000-BIS4 (< 4 years old at diagnosis with nonmetastatic medulloblastoma):
Patients receive 5 courses of cyclophosphamide, vincristine, methotrexate, carboplatin,
etoposide phosphate, and intrathecal methotrexate. Patients with residual tumors after
3 courses undergo conventionally fractionated reduced-dose radiotherapy.

- Protocol MET-HIT-2000-AB4 (≥ 4 years old at diagnosis with metastatic medulloblastoma
or supratentorial PNET): Patients receive combination chemotherapy as in HIT-2000-BIS4
for 2 courses. Patients then undergo hyperfractionated radiotherapy and receive
combination chemotherapy as in HIT-2000-AB4. Patients with good response to combination
chemotherapy (as in HIT-2000-BIS4) also receive high-dose chemotherapy.

- Protocol MET-HIT-2000-BIS4 (< 4 years old at diagnosis with metastatic medulloblastoma
or supratentorial PNET): Patients receive 2-4 courses of carboplatin IV and etoposide
phosphate IV continuously over 96 hours. Patients with partial or complete response
also receive high-dose carboplatin, etoposide phosphate, cyclophosphamide, and
thiotepa. Patients with residual tumor undergo conventional fractionated, reduced-dose
radiotherapy.

- Protocol E-HIT-2000-AB4 (≥ 4 years old at diagnosis with intracranial ependymoma):
Patients undergo local hyperfractionated radiotherapy. If histological grading shows
WHO grade III tumor, patients also receive 5 courses of vincristine, cyclophosphamide,
carboplatin, and etoposide phosphate.

- Protocol E-HIT-2000-BIS4 (< 4 years old at diagnosis with intracranial ependymoma):
Patients receive 5 courses of cyclophosphamide, vincristine, methotrexate IV,
carboplatin, and etoposide phosphate and then undergo conventional fractionated local
radiotherapy.

PROJECTED ACCRUAL: A total of 567 patients will be accrued for this study.