A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children less than 36 Months Old with Intensive Induction Chemotherapy with Methotrexate Followed by Consolidation with Stem Cell Rescue vs. the Same Therapy without Methotrexate
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given before a peripheral stem cell transplant in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma .
Age: Up to 2 years High-risk medulloblastoma Supratentorial primitive neuroectodermal tumor (PNET) MRI evidence of spinal disease Tumor must be negative for INI1 gene No atypical teratoid rhabdoid tumors
Induction therapy: Patients are randomized to 1 of 2 induction treatment arms. Arm I: Patients receive vincristine; etoposide Cyclophosphamide; cisplatin. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Arm II : Patients receive vincristine; high-dose methotrexate . Once methotrexate levels are in a safe range, patients receive etoposide ,cyclophosphamide cisplatin. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. In both arms, patients with stable disease or partial response after induction therapy proceed to second-look surgery followed by consolidation therapy. Patients with a complete response after induction therapy proceed directly to consolidation therapy. Consolidation therapy: carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 4 and continuing until blood counts recover. Patients also receive autologous peripheral blood stem cells IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Blood and tissue samples are collected at baseline for correlative studies, including gene expression profiling, biological marker analysis (i.e., cMyc, ErbB2/ErbB4), comparative genome analysis, and mutation analysis.
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