Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 16 and over NCI MICH-T87-0015 NCI-T87-0015O, T87-0015

Objectives

I.  Develop an effective intra-arterial treatment regimen (using a fully 
implantable infusion pump) of radiosensitization with broxuridine (BUDR) 
administered concomitantly with radiotherapy to patients with maximally 
resected malignant gliomas.

II.  Demonstrate that the proposed regimen can be administered with acceptable 
levels of toxicity.

III.  Study in a dose escalation protocol the incorporation of BUDR into the 
peripheral blood leukocytes and correlate the degree of incorporation with the 
plasma levels of BUDR and with myelotoxicity.

Entry Criteria

Disease Characteristics:

Biopsy-proven unilateral hemispheric glioma, including:
  Anaplastic astrocytoma
  Malignant astrocytoma
  Glioblastoma multiforme

Blood supply primarily from one carotid artery required

Measurable disease on CT scan required

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior cytotoxic chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy

Surgery:
  At least surgical biopsy required prior to entry

Patient Characteristics:

Age:
  16 and over

Performance status:
  Karnofsky 40-100%

Life expectancy:
  At least 3 months

Hematopoietic:
  WBC at least 4,000
  Platelets greater than 150,000

Hepatic:
  Bilirubin less than 2.0 mg/dl
  Alkaline phosphatase less than 2 x ULN
  SGOT less than 2 x ULN

Renal:
  Creatinine no more than 1.5 mg/dl
  BUN no more than 30 mg/dl

Other:
  No other neurologic disease that would obscure therapy
     evaluation
  Able to tolerate infusion pump placement
  No second malignancy
  No prisoners
  No pregnant women

Expected Enrollment

In the initial Phase I study, 3-6 patients were to be entered at each dose 
level of BUDR tested.  As of December 1990, a Phase I/II study to determine 
the optimum radiotherapy dose was initiated under which an additional 25 
patients will receive 70 Gy.  If 5 or more cases of radiation necrosis occur, 
accrual will stop; if 1-4 cases of radiation necrosis occur, an additional 23 
patients will be enrolled.  If toxicity is acceptable at the 70 Gy dose, 
another 25 patients will receive 80 Gy.  Accrual to the second stage is 
expected to be 15 patients/year.

Outline

Nonrandomized study.  Initially, this was a Phase I study to determine the MTD 
of BUDR radiosensitization with standard doses of radiotherapy.  Because all 
failures early in the study were due to local recurrence with no local 
radiotoxicity, the study has been expanded to a Phase I/II escalation of the 
radiotherapy dose with radiosensitization (optimum dose of BUDR).  All 
patients who progress after radiotherapy plus radiosensitization receive 
salvage therapy on Regimen A.

Radiotherapy with Single-Agent Chemotherapy/Radiosensitization.  Standard-dose 
tumor irradiation using megavoltage equipment with energies ranging from Co60 
to 10 MV photons during the BUDR dose-ranging study and high-dose tumor 
irradiation using high-energy photons or electrons with energies from 6 to 15 
MV during the radiotherapy escalation portion of the study; with Broxuridine, 
BUDR, NSC-38297.

Regimen A:  Single-Agent Salvage Chemotherapy.  Carmustine, BCNU, NSC-409962.

Trial Contact Information

Trial Lead Organizations

University of Michigan Comprehensive Cancer Center

Harry Greenberg, MD, Protocol chair		Ph: 313-936-9055; 800-865-1125 Email: hsgr@umich.edu