A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES: Primary - Compare event-free and overall survival of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with chemotherapy comprising vincristine, cisplatin, lomustine, and cyclophosphamide. - Compare event-free and overall survival of these patients (8 to 21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen. Secondary - Compare patterns of failure in patients treated with these regimens. - Compare the cognitive, auditory, and endocrinologic effects of these regimens in these patients. - Compare the audiologic and endocrinologic toxicity from these regimens in these patients. - Develop an optimal gene expression medulloblastoma outcome predictor. - Assess quality of life and functional status in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery.Patients 3 to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old are assigned to arm II. - Chemoradiotherapy:Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old are assigned to arm II. - Radiotherapy (first randomization): - Arm I: Patients undergo reduced-dose craniospinal radiotherapy with boost. - Arm II: Patients undergo standard-dose craniospinal radiotherapy with boost. All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III and IV). - Radiotherapy boost (second randomization): - Arm III: Patients will undergo radiotherapy boost to the entire posterior fossa. - Arm IV: Patients will undergo radiotherapy boost to the tumor bed only. - Maintenance chemotherapy: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration. - Regimen A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49. - Regimen B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Who is eligible to participate?

DISEASE CHARACTERISTICS: - Histologically confirmed medulloblastoma located in the posterior fossa - Standard-risk disease - Minimal volume, non-disseminated disease, defined by the following: - Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery - No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following: - Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery - Negative cytological examination of CSF after surgery, but before study enrollment - Brain stem involvement allowed PATIENT CHARACTERISTICS: Age - 3 to 21 at diagnosis Performance status - Karnofsky 50-100% (> 16 years of age) OR - Lansky 30-100% (≤ 16 years of age) Life expectancy - Not specified Hematopoietic - Absolute neutrophil count > 1,500/mm^3 - Platelet count > 100,000/mm^3 (transfusion independent) - Hemoglobin > 10 g/dL (transfusions allowed) Hepatic - Bilirubin < 1.5 times upper limit of normal (ULN) - AST or ALT < 1.5 times ULN Renal - Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy - Not specified Chemotherapy - No prior chemotherapy Endocrine therapy - Prior corticosteroids allowed Radiotherapy - No prior radiotherapy Surgery - See Disease Characteristics

Last updated:

8/12/2014

NCT ID:

NCT00085735

IRB Number:

1617-04