Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00086970
Status:
TERMINATED
Last Update Posted:
2013-01-24
First Post:
2004-07-08
Brief Title:
Ifosfamide With or Without O6-Benzylguanine in Treating Patients With Unresectable Metastatic Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
Status:
TERMINATED
Status Verified Date:
2013-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Administratively complete
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized phase I trial is studying the side effects and best dose of O6-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors Drugs used in chemotherapy such as ifosfamide and O6-benzylguanine work in different ways to stop tumor cells from dividing so they stop growing or die Combining ifosfamide with O6-benzylguanine may kill more tumor cells
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 12999B | None | None | None |
| U01CA069852 | NIH | None | None |
| CDR0000371909 | REGISTRY | PDQ Physician Data Query | httpsreporternihgovquickSearchU01CA069852 |