A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma
OBJECTIVES:
- Determine the dose of O6-benzylguanine (O6-BG) that produces total depletion of tumor
O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of patients with
cerebral anaplastic astrocytoma or glioblastoma multiforme.
- Determine the qualitative and quantitative toxicities of O6-BG in this patient
population.
OUTLINE: This is a dose escalation study.
Part I: The first cohort of 10 patients receives O6-benzylguanine (O6-BG) IV over 1 hour at
dose level 1 beginning 6 hours prior to surgery. If at least 3 of 10 patients in the first
cohort have detectable levels of O6-alkylguanine-DNA alkyltransferase (AGT), then a second
cohort of 10 patients receives O6-BG as above at dose level 2. Dose escalation continues
until at least 8 of 10 patients have undetectable AGT activity. At this point, 4 additional
patients are accrued. If at least 11 of 14 patients at this dose level have undetectable
levels of AGT, then this dose level constitutes the biologic modulatory dose of O6-BG. If
less than 11 of 14 patients have undetectable levels of AGT, then 10 additional patients are
treated at a higher dose. If at any time 3 or more patients at a dose level have detectable
AGT activity, accrual is stopped at that dose level and patients are treated at the next
higher dose level. (Part I closed to accrual effective 7/10/2000)
Part II: An additional cohort of 14 patients receives O6-BG at dose level 5 beginning 18
hours prior to surgery.
PROJECTED ACCRUAL: Part I of this study closed to accrual effective 7/10/2000. A total of 14
patients will be accrued for part II of this study at a rate of 3 patients per month.
Interventional
Primary Purpose: Treatment
Michael Prados, MD
Study Chair
UCSF Medical Center at Parnassus
United States: Federal Government
CDR0000065479
NCT00002971
April 1997
Name | Location |
---|---|
University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
Simmons Cancer Center - Dallas | Dallas, Texas 75235-9154 |
University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
University of Pittsburgh Cancer Institute | Pittsburgh, Pennsylvania 15213 |
University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |