A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard
high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in
patients treated with this regimen.
III. Determine the relationship between O6-benzylguanine dose and intra-individual
variability in the degree of myelosuppression in patients treated with this regimen.
IV. Determine the safety and toxicity of this regimen in these patients.
SECONDARY OBJECTIVES:
I. Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including
apoptosis and DNA damage, in patients treated with this regimen.
II. Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in
patients treated with this regimen.
OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of
O6-benzylguanine.
Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days
1-3.
Course 2: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive high-dose ifosfamide as in course 1.
Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1
followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on
days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus
and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12
patients experience dose-limiting toxicity.
Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in
course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all
patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood
counts recover. In all courses and in both arms, treatment repeats every 21 days in the
absence of disease progression or unacceptable toxicity.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
Baseline up to 1 year
Yes
Sonali Smith
Principal Investigator
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
NCI-2012-02601
NCT00086970
June 2004
Name | Location |
---|---|
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |