RATIONALE: Drugs used in chemotherapy, such as vinblastine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vinblastine when given together with carboplatin in treating young patients with newly diagnosed or recurrent low-grade glioma.

OBJECTIVES:

Primary

• Estimate the maximum tolerated dose and recommended phase II dose of vinblastine when given in combination with carboplatin in pediatric patients with newly diagnosed or recurrent low-grade gliomas.
• Define and describe the acute and dose-limiting toxicities of this regimen.
• Describe the toxicities associated with repeated courses of the combination chemotherapy regimen and the number of treatment modifications required over the course of treatment.

Secondary

• Describe the radiographic responses in patients treated with this regimen.
• Describe changes in diffusion/perfusion imaging during study therapy.

OUTLINE: This is a multicenter, dose-escalation study of vinblastine. Patients are stratified according to amount of prior therapy (heavily pretreated vs less heavily pretreated).

Patients receive carboplatin IV over 30 minutes on day 1 and vinblastine IV on days 1, 8, 15. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vinblastine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed* low-grade glioma, including 1 of the following subtypes:

  • Astrocytoma variants

    • Fibrillary, protoplasmic, or mixed

  • Pilocytic astrocytoma, including pilomyxoid variants

  • Pleomorphic xanthoastrocytoma

  • Infantile desmoplastic astrocytoma

  • Ganglioglioma

  • Oligodendroglial tumors

  • Mixed glioma, including oligoastrocytoma NOTE: *Biopsy not required for patients who have visual pathway tumors involving the optic nerves and/or optic radiations (i.e., not isolated to the hypothalamus/chiasm)

• Biopsy proven focal low-grade gliomas of the brainstem with measurable disease allowed

  • No diffuse, intrinsic brainstem tumors

• Residual tumor visible on MRI

• Patients without NF-1 must meet the following criteria:

  • Progressive disease after surgery/biopsy based on clear radiographic or clinical evidence of progression OR gross residual tumor (> 1.5 cm²) after surgery/biopsy that is felt to be a high risk to the patient for neurologic and/or visual impairment if the tumor progresses
  • Visual pathway tumors that are not isolated to the hypothalamus/chiasm and are not biopsied must be a high risk to the patient for neurologic and/or visual impairment

• Patients with NF-1 must have evidence of radiographic progression on MRI and/or clinical worsening (e.g., worsening of ophthalmologic exam for visual pathway tumors)

• Meets 1 of the following criteria:

  • Newly diagnosed disease
  • Recurrent disease

• No ventriculoperitoneal shunt-related ascites

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) OR Lansky PS 50-100% (for patients ≤ 10 years of age)

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³ (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age, as follows:

  • No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
  • No greater than 1.0 mg/dL (for patients 6-10 years of age)
  • No greater than 1.2 mg/dL (for patients 11-15 years of age)
  • No greater than 1.5 mg/dL (for patients > 15 years of age)

• Bilirubin ≤ 1.5 times upper limit of normal

• ALT ≤ 110 U/L

• Albumin ≥ 2 g/dL

• No history of allergy to carboplatin

• No hyponatremia requiring treatment

• No uncontrolled infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior therapy except for corticosteroids and surgery (for patients with newly diagnosed disease)
• Prior chemotherapy and/or radiotherapy in addition to surgery and corticosteroids allowed (for patients with recurrent disease)
• Prior carboplatin and/or vinblastine allowed if there was no evidence of progressive disease while on therapy and there were no dose reductions due to toxicity (for patients with recurrent disease)
• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered (for patients with recurrent disease)
• At least 7 days since prior hematopoietic growth factors (for patients with recurrent disease)
• At least 7 days since prior biological agents (for patients with recurrent disease)
• At least 9 months since prior external beam radiotherapy or gamma knife therapy that included all target lesions (i.e., there is no restriction if a new lesion arises outside the radiation field or a nonirradiated lesion progresses) and recovered (for patients with recurrent disease)
• No other concurrent investigational drugs
• No other concurrent anticancer agents
• No other concurrent chemotherapy, radiotherapy, immunotherapy, or biological therapy
• No concurrent corticosteroids for antiemesis
• Concurrent steroids allowed for tumor edema/increased intracranial pressure provided dose of dexamethasone is stable or decreasing for the past 7 days
• Concurrent physiologic or stress doses of steroids allowed for endocrine deficiencies