Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
Brief 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.
Detailed description
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.
Interventions
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed