A Phase II Trial of O6-Benzylguanine and Temozolomide in Pediatric Patients With Recurrent or Progressive High-Grade Gliomas and Recurrent or Progressive Brainstem Tumors

Inclusion Criteria

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