Trial Information

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

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.