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
Trial status: Open for Enrollment
Why is this study being done?
- 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.
- 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?
- 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
- 3 to 21 at diagnosis
- Karnofsky 50-100% (> 16 years of age) OR
- Lansky 30-100% (≤ 16 years of age)
- Not specified
- Absolute neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3 (transfusion independent)
- Hemoglobin > 10 g/dL (transfusions allowed)
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST or ALT < 1.5 times ULN
- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- Not specified
- No prior chemotherapy
- Prior corticosteroids allowed
- No prior radiotherapy
- See Disease Characteristics