Clinical trial NCT00031590
Conditions: Brain Tumors Central Nervous System Tumors Medulloblastoma
Keywords: average risk medulloblastoma craniospinal radiotherapy newly diagnosed
Sponsor: Children's Hospital of Philadelphia
Start date: 2001-04-01; Completion date: 2011-05-01
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving higher dose radiation to children with newly diagnosed average risk medulloblastoma.

Detailed description:
OBJECTIVES:

* By giving reduced dose craniospinal radiation followed by nine cycles of maintenance chemotherapy comprised of alternating cycles of lomustine, cisplatin, and vincristine alternating with cyclophosphamide and etoposide, we will reduce the late effects of higher dose radiation in children while maintaining the therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy
* To evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multi center study of reduced dose craniospinal radiotherapy and chemotherapy in patients ages 3 - 30 years with newly diagnosed average risk medulloblastoma.

* Induction chemoradiotherapy: Beginning within 28 days after complete surgical resection, patients undergo radiotherapy to the craniospinal axis (1800 centigray (cGy)) followed by conformal radiotherapy to the tumor bed (5400 cGy). Patients receive vincristine weekly for 6 weeks.
* Maintenance chemotherapy: Beginning 4 weeks after the completion of craniospinal radiation therapy, patients receive two 6-week courses of regimen A as outlined below alternating with one 6-week course of regimen B for a total of 9 courses (AABAABAAB).

  * Regimen A: Patients receive oral lomustine and cisplatin on day 0 and vincristine on days 0, 7, and 14.
  * Regimen B: Patients receive cyclophosphamide on days 0 and 1 and etoposide intravenous (IV) on days 0 and 1, followed by oral etoposide on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter with surveillance neuroimaging using Magnetic Resonance Imaging Scan (MRI scan) and clinical examination.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.

Arms: arm 1: All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide \[IV and oral\]) which will be given in the following order: AABAABAAB (total of 54 weeks).
Interventions: intervention 1: Cisplatin intervention 2: Cyclophosphamide intervention 3: Etoposide intervention 4: Lomustine intervention 5: Vincristine intervention 6: Craniospinal Radiation
Intervention descriptions: intervention 1: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). intervention 2: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Administration of cyclophosphamide will always be preceded by prehydration and Mesna (Regimen B only). intervention 3: Given at a dose of 150mg/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Given orally at a dose of 50mg/m2 as a single daily dose for 21 days beginning on day 14 of a cycle (Regimen B only). intervention 4: Given at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only). intervention 5: Given at a dose of 1.5mg/m2 given by IV infusion once a week for the first six weeks of treatment during radiation therapy. During maintenance therapy, it will be given as an IV push on days 0, 7 and 14 of each 6-week cycle (Regimen A only). intervention 6: Craniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (vincristine).

Protocol documents: