Ignite Creation Date:
2025-12-24 @ 11:38 PM
Ignite Modification Date:
2025-12-25 @ 9:28 PM
Study NCT ID:
NCT00390156
Status:
COMPLETED
Last Update Posted:
2020-07-28
First Post:
2006-10-18
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Imatinib, Bevacizumab, and Cyclophosphamide in Patients With Refractory Metastatic Solid Tumors
Sponsor:
University of California, San Francisco
Organization:
Study Overview
Official Title:
A Phase I Trial of Imatinib, Bevacizumab, & Metronomic Cyclophosphamide as Antiangiogenic Therapy in Refractory Metastatic Solid Tumors
Status:
COMPLETED
Status Verified Date:
2020-07
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: Imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell 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. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab and cyclophosphamide may also stop the growth of tumor cells by blocking blood flow to the tumor. Imatinib and bevacizumab may help cyclophosphamide work better by making tumor cells more sensitive to the drug. Giving cyclophosphamide once a day together with imatinib and bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of imatinib when given together with bevacizumab and cyclophosphamide in treating patients with refractory metastatic solid tumors.
PURPOSE: This phase I trial is studying the side effects and best dose of imatinib when given together with bevacizumab and cyclophosphamide in treating patients with refractory metastatic solid tumors.
Detailed Description:
OBJECTIVES:
Primary
* Determine the maximum tolerated dose of imatinib when given together with bevacizumab and metronomic cyclophosphamide in patients with refractory metastatic solid tumors.
* Determine the safety profile of this regimen in these patients.
Secondary
* Determine the effects of cyclophosphamide and bevacizumab on imatinib pharmacokinetics.
* Determine if patients treated with this regimen achieve plasma levels of cyclophosphamide that are predicted to be antiangiogenic.
* Determine the effects of this regimen on the number of circulating endothelial cells, endothelial progenitor cells, activated endothelial cells, and circulating tumor cells.
* Determine the effects of this regimen on parameters measured by CT scan perfusion (e.g., regional blood flow, blood volume, permeability-surface area product, and mean transit time).
OUTLINE: This is a nonrandomized, open-label, pilot, dose-escalation study of imatinib.
Patients receive oral cyclophosphamide and oral imatinib once daily on days 1-28 and bevacizumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of imatinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Primary
* Determine the maximum tolerated dose of imatinib when given together with bevacizumab and metronomic cyclophosphamide in patients with refractory metastatic solid tumors.
* Determine the safety profile of this regimen in these patients.
Secondary
* Determine the effects of cyclophosphamide and bevacizumab on imatinib pharmacokinetics.
* Determine if patients treated with this regimen achieve plasma levels of cyclophosphamide that are predicted to be antiangiogenic.
* Determine the effects of this regimen on the number of circulating endothelial cells, endothelial progenitor cells, activated endothelial cells, and circulating tumor cells.
* Determine the effects of this regimen on parameters measured by CT scan perfusion (e.g., regional blood flow, blood volume, permeability-surface area product, and mean transit time).
OUTLINE: This is a nonrandomized, open-label, pilot, dose-escalation study of imatinib.
Patients receive oral cyclophosphamide and oral imatinib once daily on days 1-28 and bevacizumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of imatinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Study Oversight
Has Oversight DMC:
True
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?: