Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00060411
Status:
COMPLETED
Last Update Posted:
2013-09-30
First Post:
2003-05-06
Brief Title:
A Phase I Pharmacological and Biological Study of OSI-774 in Combination With FOLFOX 4 5-FU Leucovorin and Oxaliplatin and Bevacizumab Avastin in Patients With Advanced Colorectal Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Pharmacological and Biological Study of OSI-774 in Combination With FOLFOX 4 5-FU Leucovorin and Oxaliplatin and Bevacizumab Avastin in Patients With Advanced Colorectal Cancer
Status:
COMPLETED
Status Verified Date:
2013-09
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:
Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth Monoclonal antibodies such as bevacizumab can block tumor growth in different ways Some block the ability of tumor cells to grow and spread Others find tumor cells and help kill them or carry tumor-killing substances to them Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die Combining erlotinib and bevacizumab with combination chemotherapy may kill more tumor cells This phase I trial is studying the side effects and best dose of erlotinib when given together with bevacizumab fluorouracil leucovorin and oxaliplatin in treating patients with metastatic or locally advanced colorectal cancer
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD of OSI-774 given in combination with FOLFOX 4 and Bevacizumab in patients with advanced colorectal cancer
II To characterize the toxicity profile of this regimen III To explore the antitumor activity of this combination
SECONDARY OBJECTIVES
I To characterize the pharmacokinetics of OSI-774 given with FOLFOX 4 and Bevacizumab
II To determine the relationship between CYP3A4 activity and OSI-774 clearance
III To correlate Cytochrome P450 activity with OSI-774 PK using midazolam clearance
IV To determine the relationship between expression and activation of the EGFR and related signaling pathways and outcome of patients with colorectal cancer patients who are treated with OSI-774 in combination with FOLFOX 4 and Bevacizumab
V To explore the biological effects of OSI-774 in patients with advanced colorectal cancer and its relationship with dose and plasma concentration
VI To explore the use of fluorodeoxy-glucose FDG positron emission tomography PET scan to predict the biological effects and outcome of patients with colorectal cancer who are treated with OSI-774 and FOLFOX 4 and Bevacizumab
VII To assess 5FU PK when given in this manner and to correlate with several previously characterized genetic polymorphisms and drug response VIII To evaluate the association of allelic variants in AAG and OSI-774 disposition
OUTLINE This is a dose-escalation study of erlotinib
Patients receive oral elotinib alone once daily for 1 week before the beginning of course 1 Patients then receive oral erlotinib once daily on days 1-28 oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2 Patients also receive bevacizumab IV over 30-90 minutes on day 15 of course 1 and on days 1 and 15 of all subsequent courses Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose MTD is determined The MTD is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity
PROJECTED ACCRUAL Approximately 38 patients will be accrued for this study within 19-38 months
I To determine the maximum tolerated dose MTD of OSI-774 given in combination with FOLFOX 4 and Bevacizumab in patients with advanced colorectal cancer
II To characterize the toxicity profile of this regimen III To explore the antitumor activity of this combination
SECONDARY OBJECTIVES
I To characterize the pharmacokinetics of OSI-774 given with FOLFOX 4 and Bevacizumab
II To determine the relationship between CYP3A4 activity and OSI-774 clearance
III To correlate Cytochrome P450 activity with OSI-774 PK using midazolam clearance
IV To determine the relationship between expression and activation of the EGFR and related signaling pathways and outcome of patients with colorectal cancer patients who are treated with OSI-774 in combination with FOLFOX 4 and Bevacizumab
V To explore the biological effects of OSI-774 in patients with advanced colorectal cancer and its relationship with dose and plasma concentration
VI To explore the use of fluorodeoxy-glucose FDG positron emission tomography PET scan to predict the biological effects and outcome of patients with colorectal cancer who are treated with OSI-774 and FOLFOX 4 and Bevacizumab
VII To assess 5FU PK when given in this manner and to correlate with several previously characterized genetic polymorphisms and drug response VIII To evaluate the association of allelic variants in AAG and OSI-774 disposition
OUTLINE This is a dose-escalation study of erlotinib
Patients receive oral elotinib alone once daily for 1 week before the beginning of course 1 Patients then receive oral erlotinib once daily on days 1-28 oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2 Patients also receive bevacizumab IV over 30-90 minutes on day 15 of course 1 and on days 1 and 15 of all subsequent courses Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose MTD is determined The MTD is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity
PROJECTED ACCRUAL Approximately 38 patients will be accrued for this study within 19-38 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-2012-03157 | REGISTRY | None | None |
| NCI-5869 | None | None | None |
| JHOC-J0220 | None | None | None |
| JHOC-02072506 | None | None | None |
| J0220 02-07-25-06 | OTHER | None | None |
| 5869 | OTHER | None | None |
| U01CA070095 | NIH | CTEP | httpsreporternihgovquickSearchU01CA070095 |