Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002604
Status:
COMPLETED
Last Update Posted:
2010-07-08
First Post:
1999-11-01
Brief Title:
O6-Benzylguanine and Carmustine in Treating Patients With Solid Tumors
Sponsor:
Case Comprehensive Cancer Center
Organization:
Case Comprehensive Cancer Center
Study Overview
Official Title:
Phase I Trial of O6 Benzylguanine and BCNU A Biochemical Modulation Trial Based Upon Depletion of O6 Alkylguanine DNA Alkyltransferase Directed DNA Repair
Status:
COMPLETED
Status Verified Date:
2010-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die Combining more than one drug may kill more tumor cells
PURPOSE Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating patients who have solid tumors
PURPOSE Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating patients who have solid tumors
Detailed Description:
OBJECTIVES I Determine the biochemical modulation dose l of O6-benzylguanine BG defined as the dose at which baseline O6-alkylguanine DNA alkyltransferase AGT activity in circulating peripheral blood mononuclear cells PBMC decreases by greater than 90 in patients with advanced solid tumors at 2 hours after BG infusion II Determine the biochemical modulation dose t18 BMDt18 of BG defined as the dose at which AGT activity in human metastatic tumor tissue decreases to undetectable levels at 18 hours after BG infusion III Determine the maximum tolerated dose of carmustine BCNU when administered with BG at the BMDt18 in these patients IV Determine the toxicities of BG and BCNU in these patients V Determine the pharmacokinetic parameters of BG administered at the BMDt18 and determine any effects of BCNU on BG pharmacokinetics VI Assess any antitumor response in patients with metastatic solid tumors treated with this regimen VII Determine the effect of lower more frequent bolus doses or a continuous infusion of BG on the depletion of AGT activity in PBMC and tumor tissue in these patients VIII Determine the pharmacokinetics of BG in lower more frequent bolus doses or continuous infusion
OUTLINE This is a dose escalation study of 06-benzylguanine BG and carmustine BCNU Patients receive BG IV over 1 hour during week 1 and then BG IV over 1 hour followed 1 hour later by BCNU IV over 1 hour during week 3 Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity Cohorts of 1-3 patients receive escalating doses of BG until the biochemical modulation dose l BMDl is determined The BMDl is defined as the dose at which baseline O6-alkylguanine DNA alkyltransferase AGT activity in circulating peripheral blood mononuclear cells decreases by greater than 90 at 2 hours after BG infusion Cohorts of 3 patients receive escalating doses of BG beginning at the BMDl until the biochemical modulation dose t2 BMDt2 is determined The BMDt2 is defined as the dose at which AGT activity in human metastatic tumor tissue decreases by greater than 90 at 2 hours after BG infusion Cohorts of 3 patients receive escalating doses of BG beginning at the BMDt2 until the biochemical modulation dose t18 BMDt18 is determined The BMDt18 is defined as the dose at which AGT activity in human metastatic tumor tissue decreases to undetectable levels at 18 hours after BG infusion Patients then receive BG IV over 1 hour followed 1 hour later by BCNU IV over 1 hour during week 1 Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of BCNU combined with BG at the BMDt18 until the maximum tolerated dose MTD of BCNU is determined The MTD of BCNU is defined as the dose preceding that at which 2 or more of 6 patients experience dose limiting toxicity A cohort of 3 patients receives BG IV over 2 minutes and another cohort of 3 patients receives BG IV over 24 hours An additional cohort of 6 patients receives BG IV over 24 hours and BCNU IV over 1 hour beginning 2 hours into BG infusion during week 3
PROJECTED ACCRUAL A total of 51 patients will be accrued for this study over 36 months
OUTLINE This is a dose escalation study of 06-benzylguanine BG and carmustine BCNU Patients receive BG IV over 1 hour during week 1 and then BG IV over 1 hour followed 1 hour later by BCNU IV over 1 hour during week 3 Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity Cohorts of 1-3 patients receive escalating doses of BG until the biochemical modulation dose l BMDl is determined The BMDl is defined as the dose at which baseline O6-alkylguanine DNA alkyltransferase AGT activity in circulating peripheral blood mononuclear cells decreases by greater than 90 at 2 hours after BG infusion Cohorts of 3 patients receive escalating doses of BG beginning at the BMDl until the biochemical modulation dose t2 BMDt2 is determined The BMDt2 is defined as the dose at which AGT activity in human metastatic tumor tissue decreases by greater than 90 at 2 hours after BG infusion Cohorts of 3 patients receive escalating doses of BG beginning at the BMDt2 until the biochemical modulation dose t18 BMDt18 is determined The BMDt18 is defined as the dose at which AGT activity in human metastatic tumor tissue decreases to undetectable levels at 18 hours after BG infusion Patients then receive BG IV over 1 hour followed 1 hour later by BCNU IV over 1 hour during week 1 Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of BCNU combined with BG at the BMDt18 until the maximum tolerated dose MTD of BCNU is determined The MTD of BCNU is defined as the dose preceding that at which 2 or more of 6 patients experience dose limiting toxicity A cohort of 3 patients receives BG IV over 2 minutes and another cohort of 3 patients receives BG IV over 24 hours An additional cohort of 6 patients receives BG IV over 24 hours and BCNU IV over 1 hour beginning 2 hours into BG infusion during week 3
PROJECTED ACCRUAL A total of 51 patients will be accrued for this study over 36 months
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 |
|---|---|---|---|
| NCI-T94-0022D | US NIH GrantContract | None | httpsreporternihgovquickSearchU01CA062502 |
| U01CA062502 | NIH | None | None |
| CWRU-ICC-1994 | None | None | None |