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Phase I/II Study of Pyrazoloacridine (PZA) in Adults With Newly Diagnosed Glioblastoma Multiforme

Phase 1/Phase 2
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

Phase I/II Study of Pyrazoloacridine (PZA) in Adults With Newly Diagnosed Glioblastoma Multiforme


- 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.

Inclusion Criteria


- 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



- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- Not specified


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

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


- Bilirubin no greater than 1.5 mg/dL

- Transaminases no greater than 4 times upper limit of normal


- Creatinine no greater than 1.7 mg/dL


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

- 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


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


- 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


- No prior radiotherapy for glioblastoma multiforme


- See Disease Characteristics

- Recovered from immediate postoperative period


- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Glenn J. Lesser, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Comprehensive Cancer Center of Wake Forest University


United States: Food and Drug Administration

Study ID:

NABTT-9804 CDR0000068223



Start Date:

May 2000

Completion Date:

October 2006

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
University of Alabama at Birmingham Comprehensive Cancer Center Birmingham, Alabama  35294-3300
Comprehensive Cancer Center at Wake Forest University Winston-Salem, North Carolina  27157-1082
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
Josephine Ford Cancer Center at Henry Ford Health System Detroit, Michigan  48202