Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically proven, newly diagnosed, supratentorial, grade IV astrocytoma (glioblastoma multiforme) - Incompletely resected disease.

• - Must have measurable and contrast enhancing tumor on the postoperative MRI/CT scan.

PATIENT CHARACTERISTICS: Age:

• - 18 and over.

Performance status:

• - Karnofsky 60-100% Life expectancy: - Not specified.

Hematopoietic:

• - Absolute neutrophil count at least 1,500/mm^3.

• - Platelet count at least 100,000/mm^3.

Hepatic:

• - Bilirubin no greater than 1.5 mg/dL.

• - Transaminases no greater than 4 times upper limit of normal.

Renal:

• - Creatinine no greater than 1.7 mg/dL.

Other:

• - No other serious concurrent infection or medical illness that would preclude study therapy.

• - No other active malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell skin cancer.

• - No psychosis requiring ongoing therapy with antipsychotic medication.

• - Mini mental score at least 15.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

PRIOR CONCURRENT THERAPY: Biologic therapy:

• - No prior immunotherapy or biologic agents (including immunotoxins, immunoconjugates, antisense compounds, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes, lymphokine activated killer cells, or gene therapy) for glioblastoma multiforme.

• - No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) Chemotherapy: - No prior chemotherapy for glioblastoma multiforme.

Endocrine therapy:

• - No prior hormonal therapy for glioblastoma multiforme.

• - Prior glucocorticoids allowed.

• - Concurrent corticosteroids allowed if on stable dose (no increase within the past 5 days) Radiotherapy: - No prior radiotherapy for glioblastoma multiforme.

Surgery:

• - See Disease Characteristics.

• - Recovered from immediate postoperative period.

Other: - Greater than 10 days since prior anticonvulsants that induce hepatic metabolic enzymes (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or felbamate) - No other concurrent investigational agents

OBJECTIVES:

• - Determine the maximum tolerated dose, toxicity, and pharmacokinetics of pyrazoloacridine in adults with newly diagnosed, supratentorial glioblastoma multiforme treated with pyrazoloacridine followed by radiotherapy.

• - Determine the response rate, duration of disease free survival, and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to type of anticonvulsant (hepatic metabolic enzyme inducers vs.#46;hepatic metabolic enzyme moderate inducers or noninducers). Patients receive pyrazoloacridine (PZA) IV over 3 hours on day 1. Treatment repeats every 3 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Following completion of PZA treatment, patients undergo cranial irradiation 5 days a week for 6 weeks. Cohorts of 3 patients receive escalating doses of PZA until the maximum tolerated dose (MTD) is determined. Additional patients receive PZA at the MTD. Patients are followed monthly for survival. PROJECTED ACCRUAL: A minimum of 3 patients will be accrued for phase I and a total of 18-35 patients will be accrued for phase II of this study.