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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Radiation: radiation therapy; Procedure: adjuvant therapy; Drug: pyrazoloacridine

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Glenn J. Lesser, MD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• 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, 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (Actual): October 1, 2004
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: October 4, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 3, 2012
• Last Update Submitted That Met QC Criteria: May 1, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Antineoplastic Agents; NSC 366140
• Other Study ID Numbers: NABTT-9804 CDR0000068223; P30CA006973 (U.S. NIH Grant/Contract); U01CA062475 (U.S. NIH Grant/Contract); NABTT-9804; JHOC-NABTT-9804