Phase I GLIADEL and Continuous Infusion of Intravenous O6-Benzylguanine Trial in Patients With Recurrent Malignant Glioma
OBJECTIVES: I. Determine the dose of O6-benzylguanine that completely suppresses AGT levels
in patients with recurrent malignant glioma. II. Evaluate the safety and tolerance of
increasing duration for up to 2 weeks of continuously infused O6-benzylguanine at a dose
that will completely suppress tumor AGT activity combined with intracranially implanted
polifeprosan 20 with carmustine implants (Gliadel wafers) in this patient population.
OUTLINE: This is a dose escalation study of O6-benzylguanine (O6-BG). Patients in the first
cohort receive O6-BG IV over 1 hour followed by continuous infusion of O6-BG for 2 days
prior to surgery. Patients undergo surgical resection and receive up to 8 polifeprosan 20
with carmustine implants (Gliadel wafers) in the resected tumor cavity. Cohorts of 14
patients receive escalating doses of O6-BG until 11 out of 14 patients in a cohort have
complete suppression of AGT levels. Once the dose of O6-BG that completely suppresses AGT
has been established, subsequent patients receive O6-BG IV beginning at least 1 hour prior
to surgery followed by the established continuous infusion dose beginning on the day of
surgery. The infusion continues for up to 14 days postoperatively. Cohorts of 6-12 patients
receive lengthened durations of continuous infusion O6-BG until the maximum tolerated dose
(MTD) is determined or the length of the infusion reaches 14 days. The MTD is defined as the
dose preceding that at which 3 of 6 or 5 of 12 patients experience dose limiting toxicities.
Patients are followed at 3, 6, 9, and 12 months, and then until death.
PROJECTED ACCRUAL: A minimum of 38 patients will be accrued for this study over 9.5 months.
Primary Purpose: Treatment
Jon Weingart, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|University of Alabama Comprehensive Cancer Center||Birmingham, Alabama 35294|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Emory University Hospital - Atlanta||Atlanta, Georgia 30322|
|Johns Hopkins Oncology Center||Baltimore, Maryland 21287|
|Comprehensive Cancer Center of Wake Forest University Baptist Medical Center||Winston-Salem, North Carolina 27157-1082|
|University of Pennsylvania Cancer Center||Philadelphia, Pennsylvania 19104|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Henry Ford Hospital||Detroit, Michigan 48202|