Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Pyrazoloacridine Followed by Radiation Therapy in Treating Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme

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.

Eligibility: 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

Relevance to patient case: not relevant