Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
Unspecified Adult Solid Tumor, Protocol Specific
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors|
- Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia [ Time Frame: Baseline up to 1 year ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]DLT is defined as any >= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.
- Pharmacodynamics including apoptosis and DNA damage [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- Pharmacokinetics of O6-benzylguanine [ Time Frame: Up to day 3 of course 2 ] [ Designated as safety issue: No ]Summarized using descriptive statistics (mean, median, standard deviation, and interquartile range). Estimated via nonlinear regression.
|Study Start Date:||June 2004|
|Primary Completion Date:||November 2005 (Final data collection date for primary outcome measure)|
Experimental: Arm I (ifosfamide)
Patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Experimental: Arm II (O6-benzylguanine, ifosfamide)
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.
Other Names:Drug: O6-benzylguanine
Other Name: BG
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00086970
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637-1470|
|Principal Investigator:||Sonali Smith||University of Chicago Comprehensive Cancer Center|