Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
Trial Purpose and Description
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy combined with chemotherapy after surgery is more effective than reduced-dose craniospinal (head and spine) radiation therapy plus either posterior fossa (back of the brain) boost or tumor bed (site of the tumor) boost radiation therapy combined with chemotherapy in treating medulloblastoma.
PURPOSE: This randomized phase III trial is studying standard-dose radiation therapy to see how well it works compared to reduced-dose craniospinal radiation therapy AND posterior fossa boost radiation therapy to see how well it works compared to tumor bed boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma.
- 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
- Compare the audiologic and endocrinologic toxicity from these regimens in these
- 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
- Radiotherapy boost (second randomization):
- Arm III: Patients will undergo radiotherapy boost to the entire posterior
- 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
- 3 Years - 21 Years
- 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
- 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
- Negative cytological examination of CSF after surgery, but before study
- 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
- Children's Oncology Group
- National Cancer Institute (NCI)
- April 2004
- Last Updated:
- June 6, 2013
- Study HIC#:
Clinicaltrials.gov ID: NCT00085735