Clinical trial NCT00006355: Pyrazoloacridine Followed by Radiation Therapy in Treating Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme
Official title: Phase I/II Study of Pyrazoloacridine (PZA) in Adults With Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Health System
state: Michigan
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Wake Forest University Health Sciences
name: Glenn J. Lesser, MD
role: STUDY_CHAIR
References:
citation: Frenay M, Lebrun C, Fontaine D, et al.: First-line chemotherapy in non resectable low-grade astrocytomas in adults. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-2095, 71b, 2002.
citation: Lesser GJ, Carson K, Supko J, et al.: A phase I/II trial and pharmacokinetic study of pyrazoloacridine in adults with newly diagnosed glioblastoma multiforme. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-485, 121a, 2003.
citation: Lesser GJ, Carson K, Priet R, et al.: A phase I/II trial of pyrazoloacridine (PZA) in adults with newly diagnosed glioblastoma multiforme (GBM). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-2097, 2002.