OBJECTIVES:
- Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.
- Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.
- Assess the feasibility of harvesting PBSCs in these patients.
- Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter study.
Patients undergo surgery for diagnosis and maximal tumor resection.
Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.
Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.
PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.
DISEASE CHARACTERISTICS:
- Histologically proven malignant brain or spinal cord tumor, including the following:
- Primitive neuroectodermal tumor
- Ganglioneuroblastoma
- Medulloblastoma neuroblastoma
- Desmoplastic medulloblastoma
- Medulloepithelioma
- Ependymoma neuroepithelioma
- Anaplastic ependymoma germ cell tumor
- Astrocytoma germinoma
- Anaplastic astrocytoma
- Embryonal carcinoma
- Glioblastoma endodermal sinus tumor
- Gliosarcoma malignant teratoma
- Choroid plexus carcinoma
- Mixed germ cell tumor
- Cerebellar sarcoma
- Pineoblastoma
- Atypical teratoid/rhabdoid tumor
- Choriocarcinoma
- Teratoma (malignant or with malignant transformations)
- Diffusely involved brain stem tumors allowed if there is evidence of brain stem glioma by CT scan or MRI
PATIENT CHARACTERISTICS:
Age:
- 6 months to less than 3 years
Performance Status:
- Not specified
Life Expectancy:
- More than 8 weeks
Hematopoietic:
- Absolute neutrophil count greater than 1,000/mm^3
- Platelet count greater than 100,000/mm^3
Hepatic:
- Bilirubin less than 2.0 mg/dL
Renal:
- Glomerular filtration rate or creatinine clearance greater than 70 mL/min
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior biologic therapy
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Prior corticosteroids allowed
Radiotherapy:
- No prior radiotherapy
Surgery:
- No more than 6 weeks since prior surgery
- Recovered from prior surgery (stable)
Last updated: 05/15/2013
NCT ID: NCT00003141
IRB Number:855-98
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