The purpose of this study is to improve overall survival while maintaining a good quality of life in pediatric patients with refractory or recurrent brain tumors (medulloblastomas, supratentorial PNETs, ependymomas WHO grade II and III). Response to different chemotherapy options (intravenous versus oral chemotherapy, intraventricular chemotherapy) as part of a multimodal therapy will be assessed. Progression-free, overall survival and toxicity will be evaluated additionally.

Parts of the study:

P-HIT-REZ-2005: a trial for the treatment of relapsed PNETs (medulloblastomas,supratentorial PNETs)

E-HIT-REZ-2005: a trial for the treatment of relapsed ependymomas (Phase II-Study with temozolomide)

Phase II-Study: intraventricular therapy with etoposide in neoplastic meningitis in relapsed PNETs and ependymomas with subarachnoid tumor manifestation (window study)

Inclusion Criteria:

Disease Characteristics

• Histologically confirmed Medulloblastoma, cerebral PNET or Ependymoma
• Refractory or relapsed disease
• Measurable disease by MRI or detection of tumor cells in cerebrospinal fluid Patients characteristics
• Performance status ECOG ≥ 3 or Karnofsky Status ≥ 40%
• Life expectancy ≥ 8 weeks

Hematological:

• Absolute leukocyte count ≥ 2.0 x 10^9 /l
• Hemoglobin ≥ 10g/dl
• Platelet count ≥ 70 x 10^9/l

Renal:

• Creatinine no greater than 1.5 times UNL
• No overt renal disease

Hepatic:

• Bilirubin less than 2.5 times UNL
• AST and ALT less than 5 times UNL
• No overt hepatic disease

Pulmonary:

• No overt pulmonary disease

Cardiovascular:

• No overt cardiovascular disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection Prior concurrent therapy
• More than 2 weeks since prior systemic chemotherapy
• More than 4 weeks since prior radiotherapy
• No other concurrent anticancer or experimental drugs Examinations required
• Examination of lumbar CSF
• Cranial and spinal MRI within 14 days prior to start of treatment