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

Conditions

Brain Tumor | Central Nervous System Tumor

Trial Phase

Phase 3

Trial Purpose and Description

Trial Purpose

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.


Trial Description


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.

Participation Guidelines

Age:
3 Years - 21 Years
Gender:
Both

Eligibility Criteria


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
Sponsor:
Children's Oncology Group
National Cancer Institute (NCI)
Dates:
April 2004
Last Updated:
June 6, 2013
Study HIC#:

Clinicaltrials.gov ID: NCT00085735