This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the sustained objective response rate to the combination of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brain stem tumors.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (high-grade gliomas vs brain stem tumors).

Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed to the earliest of 30 days following discontinuation of therapy or the initiation of additional anti-cancer therapy or death.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

INCLUSION CRITERIA

• Tumor: Participants must have a high-grade glioma (including e.g. histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic confirmation waived) with documentation of disease recurrence or progression after treatment with standard therapy. Participants must have bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions
• Age: 21 years of age or less
• Performance status: Karnofsky 60-100% (for patients > 16 years of age) or Lansky 60-100% (for patients ≤ 16 years of age)
• Life expectancy: Not specified
• Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL (may be supported), and absolute lymphocyte count ≥ 500/mm^3
• Hepatic: Must have SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN, and no overt hepatic disease
• Renal: Participants must have creatinine clearance ≥ 60 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 to 10 years of age), no greater than 1.2 mg/dL (for patients 11 to 15 years of age), or no greater than 1.5 mg/dL (for patients > 15 years of age). There must be no overt renal disease
• Cardiovascular: Must have no overt cardiac disease
• Pulmonary: Must have no overt pulmonary disease
• Other: Female participants of childbearing potential must have a negative pregnancy test prior to study registration, and must avoid breast-feeding. Female and male participants of childbearing or child-fathering potential must use effective contraception
• Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow transplantation and at least 3 months since prior autologous bone marrow or stem cell transplantation
• Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)
• Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer chemotherapy ≥ 3 weeks prior to study registration and ≥ 6 weeks for nitrosoureas. Must have received last dose of nonmyelosuppressive investigational agents or anticancer drugs ≥ 7 days prior to study registration. Participants who have received prior temozolomide are eligible
• Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed
• Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and local irradiation to the primary tumor ≥ 12 weeks prior to study registration
• Prior Therapy-Other: Must have recovered from all prior therapy

EXCLUSION CRITERIA

• Must not have history of severe toxicity (≥ grade 3) associated with temozolomide
• Must not be receiving other concurrent anticancer or investigational therapy
• Must not have history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG)
• Must not have uncontrolled significant systemic illness including infection, or overt renal, hepatic, cardiac, or pulmonary disease
• Must not be HIV positive