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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00006355

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: pyrazoloacridine Procedure: adjuvant therapy Radiation: radiation therapy	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2000

Actual Primary Completion Date :

Oct 1, 2004

Actual Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3295
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
3	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
4	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231
5	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114-2617
6	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan	United States	48202
7	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1030
8	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283