Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma

OBJECTIVES:

Primary

- Determine the feasibility and toxicity of an induction and maintenance regimen
comprising carboplatin, vincristine, and temozolomide in children with progressive
and/or symptomatic low-grade gliomas.

Secondary

- Determine response rate in patients treated with this regimen.

- Determine 3-year progression-free survival and overall survival of patients treated with
this regimen.

- Correlate response and progression-free survival with the genomic profile of tumors in
patients treated with this regimen.

OUTLINE: This is a pilot study.

- Induction therapy: Patients receive carboplatin IV over 1 hour on days 1, 8, 15, and 22;
vincristine IV on days 1, 8, 15, 22, 29, and 36; and oral temozolomide on days 43-47.
Four weeks after the completion of induction therapy, patients achieving stable or
responding disease proceed to maintenance therapy.

- Maintenance therapy: Patients receive carboplatin and temozolomide as in induction
therapy and vincristine IV on days 1, 8, and 15. Treatment repeats every 10 weeks for a
total of 6 courses in the absence of disease progression.

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

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed progressive and/or symptomatic low-grade glioma, including
any of the following:

- WHO grade I or II astrocytoma

- Grade I or II oligodendrogliomas

- Mixed oligodendrogliomas

- Gangliogliomas

- Measurable disease

- Progressive and/or symptomatic supratentorial or spinal cord tumors that cannot be
removed for anatomical reasons are allowed

- Optic pathway tumors allowed provided there is evidence of progressive disease by MRI
and/or symptoms of deteriorating vision, progressive hypothalamic/pituitary
dysfunction, or diencephalic syndrome

- Dorsally exophytic brainstem gliomas that were previously resected more than 50% are
allowed provided the residual tumor shows progression (with or without symptoms)

- No diffuse brain stem tumors

- No type 1 neurofibromatosis

PATIENT CHARACTERISTICS:

Age

- 10 and under

Performance status

- ECOG 0-2

- Lansky 50-100%

Life expectancy

- Not specified

Hematopoietic

- Hemoglobin ≥ 8.0 gm/dL

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT < 2.5 times ULN

Renal

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

- Creatinine ≤ 0.8 mg/dL (age 5 and under) OR ≤ 1.0 mg/dL (age 6 to10)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 2 months after study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunomodulating agents

Chemotherapy

- No other concurrent anticancer chemotherapy

Endocrine therapy

- Prior corticosteroids allowed

- No concurrent corticosteroids except for the treatment of increased intracranial
pressure

Radiotherapy

- Not specified

Surgery

- See Disease Characteristics

- Prior surgery allowed

Other

- No other prior therapy