Clinical Trials

Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma

Location:

Rochester,  MN

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: 11/22/2012

NCT ID:

NCT00085735