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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006355
• Other study ID #: NABTT-9804 CDR0000068223
• Secondary ID: U01CA062475P30CA
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 4, 2000
• Last updated: May 1, 2012
• Start date: May 2000
• Est. completion date: October 2006

Study information

• Verified date: May 2012
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: October 2006
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• pyrazoloacridine

Procedure:
• adjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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.

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.

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.