Phase I/II Study of Pyrazoloacridine (PZA) in Adults With Newly Diagnosed Glioblastoma Multiforme
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Phase I/II Study of Pyrazoloacridine (PZA) in Adults With Newly Diagnosed 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.
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Glenn J. Lesser, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Comprehensive Cancer Center of Wake Forest University
Authority:
United States: Food and Drug Administration
Study ID:
NABTT-9804 CDR0000068223
NCT ID:
NCT00006355
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
Name | Location |
|---|---|
| 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 |
