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DISEASE CHARACTERISTICS:

• - Histologically confirmed glioblastoma multiforme (GBM), including the following: - Small or large cell GBM.

• - Gliosarcoma.

• - Temozolomide-resistant disease, as defined by the following: - Unequivocal evidence of tumor progression after receiving adjuvant temozolomide therapy for 5 consecutive days every 28 days for ≥ 2 courses.

• - Must have failed prior radiotherapy.

• - Progression must be documented by MRI (while on a stable steroid dose for ≥ 5 days) ≥ 12 weeks after completion of radiotherapy.

• - Must have paraffin-embedded tissue blocks or ≥ 4 unstained paraffin-embedded microscope slides available from diagnosis.

PATIENT CHARACTERISTICS:

• - Karnofsky performance status 60-100% - Life expectancy > 8 weeks.

• - White blood cell (WBC) ≥ 3,000/mm(³) - Absolute neutrophil count ≥ 1,500/mm(³) - Platelet count ≥ 100,000/mm(³) - Hemoglobin ≥ 10 g/dL (transfusion allowed) - Aspartate aminotransaminase (AST) < 2 times upper limit of normal (ULN) - Bilirubin < 2 times ULN.

• - Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min.

• - No significant medical illness that, in the opinion of the investigator, would preclude study compliance.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - No significant active cardiac, hepatic, renal, or psychiatric disease.

• - No other known active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix.

• - No active infection requiring intravenous (IV) antibiotics.

• - No disease that would obscure toxicity or alter drug metabolism.

PRIOR CONCURRENT THERAPY:

• - See Disease Characteristics.

• - Recovered from prior temozolomide.

• - Prior resection of recurrent or progressive tumor allowed if all the following criteria are met: - Recovered from prior surgery.

• - Residual disease after resection of recurrent tumor by computed tomography (CT) scan or magnetic resonance imaging (MRI) (while on a stable steroid dose for ≥ 5 days) ≤ 96 hours OR ≥ 4 weeks after surgery.

• - At least 12 weeks since prior radiotherapy.

- No other prior therapy (i.e., polifeprosan 20 with carmustine implant [Gliadel wafers] or nitrosoureas) - No other concurrent chemotherapy, radiotherapy, immunotherapy, or investigational agents

OBJECTIVES:

• - Determine the antitumor activity of O6-benzylguanine and temozolomide in patients with temozolomide-resistant methylguanine methyltransferase-positive or -negative glioblastoma multiforme previously treated with radiotherapy.

• - Determine, preliminarily, the toxicity of this regimen in these patients.

OUTLINE: Patients receive O6-benzylguanine intravenous (IV) over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for at least 6 months. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Arms

Experimental: O6-benzylguanine & Temozolomide in Glioblastoma

Patients receive O6-benzylguanine intravenous over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - O6-benzylguanine

Drug: - temozolomide