Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System with Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation
This phase III trial is studying giving combination chemotherapy together with 3-dimensional conformal radiation therapy and an autologous peripheral blood stem cell transplant to see how well it works in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system.
Ages : up to 21 Years Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT) Patients with extraneural metastasis (M4) or renal rhabdoid tumors are not eligible Patients with MRI evidence of spinal disease are eligible Must have undergone definitive surgery in the past 31 days Cranial MRI (with and without gadolinium) must be done pre-operatively Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28 days after surgery Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10- 28 days after surgery), prior to study enrollment (with and without gadolinium)
Induction therapy and stem cell harvest: Patients receive vincristine IV on days 1, 8, and 15 and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of methotrexate, patients receive leucovorin calcium orally or IV every 6 hours until the serum methotrexate level is less than 0.1 micromoles. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing until ANC recovers. When ANC is greater than 1,000/Î¼L post nadir, patients receive G-CSF twice daily for stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are harvested once daily, as needed, after each course of induction therapy until a total of 15 x 10^6 CD34+ cells/kg have been collected. Treatment repeats every 21 days for 2 courses. After completion of induction therapy, patients are re-evaluated. Patients with progressive disease are removed from study. Patients with radiographic evidence of residual tumor are encouraged to undergo second-look surgery prior to proceeding to radiotherapy or consolidation therapy; patients with complete response, partial response, or stable disease proceed to radiation therapy or consolidation therapy depending on age, location of the tumor, and initial diagnosis (whether or not disease is disseminated).** Consolidation therapy and stem cell rescue: Within 2-6 weeks after completion of induction therapy or radiation therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over 4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous peripheral blood stem cell rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily beginning 24 hours after stem cell infusion and continuing until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Radiation therapy: *Before (but after induction therapy) or after consolidation therapy and stem cell rescue, patients undergo 3-dimensional conformal radiotherapy to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
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