NCT00031590

Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma

Study Of Reduced Dose Craniospinal Radiotherapy (1800 cGy) And Chemotherapy In Children With Newly-Diagnosed Standard-Risk Posterior Fossa Primitive Neuro-ectodermal Tumor (PNET/Medulloblastoma)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Children's Hospital of Philadelphia · Academic / Other
• Sex: All
• Age: 3 Years – 30 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Brain Tumors
• Central Nervous System Tumors
• Medulloblastoma

Interventions

Type	Name	Description
DRUG	Cisplatin	Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only).
DRUG	Cyclophosphamide	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).
DRUG	Etoposide	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).
DRUG	Lomustine	Given at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only).
DRUG	Vincristine	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).
RADIATION	Craniospinal Radiation	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).

Timeline

• Start date: 2001-04-01
• Primary completion: 2011-05-01
• Completion: 2011-05-01
• First posted: 2003-01-27
• Last updated: 2019-04-25
• Results posted: 2019-04-25

Locations

3 sites across 1 country: United States