pyrazoloacridine followed by radiation therapy in treating adults with newly diagnosed supratentorial glioblastoma multiforme

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. combining chemotherapy and radiation therapy may kill more tumor cells. purpose: phase i/ii trial to study the effectiveness of pyrazoloacridine followed by radiation therapy in treating adults who have newly diagnosed supratentorial glioblastoma multiforme.

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 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.

Eligibility criteria:
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

Keywords: adult glioblastoma adult giant cell glioblastoma adult gliosarcoma