Pyrazoloacridine Followed by Radiation Therapy in Treating Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme
Pyrazoloacridine Followed by Radiation Therapy in Treating Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme
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.
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