Etoposide Plus Radiation Therapy Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed Advanced Medulloblastoma

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Central Nervous System Tumors; Brain Tumors

Treatments: Drug: vincristine sulfate; Drug: cyclophosphamide; Radiation: radiation therapy; Biological: filgrastim; Drug: cisplatin; Drug: etoposide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003573

9631

CDR0000066640 (Other Identifier)

POG-9631 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of etoposide plus radiation therapy followed by combination chemotherapy in treating children with newly diagnosed advanced medulloblastoma.

Full description

OBJECTIVES:

• Assess the response rate and toxicity of oral etoposide and radiotherapy in children with newly diagnosed high stage medulloblastoma.
• Compare the response rate and toxicity of these patients to historical control patients registered on POG #9031.
• Estimate the 2-year event-free survival and overall survival of these patients.
• Evaluate the toxicity of dose intensive chemotherapy with oral etoposide, cisplatin, cyclophosphamide, and vincristine following craniospinal irradiation in these patients.

OUTLINE: Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiotherapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7).

Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and annually thereafter.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within about 2 years.

Enrollment: 53 patients

Sex: All

Ages: 3 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically diagnosed advanced (high grade) childhood medulloblastoma
• Residual disease of at least 1.5 cm2 in size on MRI or CT scan OR
• Evidence of CNS or extraneural metastases

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• SGPT less than 5 times normal
• Bilirubin less than 1.5 mg/dL

Renal:

• Creatinine less than 1.7 mg/dL OR
• Creatinine clearance greater than 70 mL/min

Other:

• Not pregnant or nursing
• 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:

• Not specified

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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53 participants in 2 patient groups

Treatment 1, Etoposide, 50mg/m2/day

Experimental group

Description:

Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiation therapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7). Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Treatment:

Drug: etoposide

Drug: cisplatin

Biological: filgrastim

Drug: cyclophosphamide

Radiation: radiation therapy

Drug: vincristine sulfate

Treatment 2, Etoposide, 35mg/m2/day

Experimental group

Description:

Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiation therapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7). Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Treatment:

Drug: etoposide

Drug: cisplatin

Biological: filgrastim

Drug: cyclophosphamide

Radiation: radiation therapy

Drug: vincristine sulfate