Ignite Creation Date:
2024-05-05 @ 5:13 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00410956
Status:
COMPLETED
Last Update Posted:
2024-05-09
First Post:
2006-12-11
Brief Title:
Floxuridine and Dexamethasone as a Hepatic Arterial Infusion and Bevacizumab in Treating Patients With Primary Liver Cancer That Cannot be Removed by Surgery
Sponsor:
Memorial Sloan Kettering Cancer Center
Organization:
Memorial Sloan Kettering Cancer Center
Study Overview
Official Title:
A Phase II Study of Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Intravenous Bevacizumab A Monoclonal Antibody to Vascular Endothelial Growth Factor-A in Patients With Unresectable Primary Hepatic Malignancy
Status:
COMPLETED
Status Verified Date:
2024-05
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 such as floxuridine and dexamethasone work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing 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 tumor cells by blocking blood flow to the tumor Giving chemotherapy directly into the arteries around the tumor together with bevacizumab may kill more tumor cells
PURPOSE This phase II trial is studying how well giving floxuridine and dexamethasone as a hepatic arterial infusion together with bevacizumab works in treating patients with unresectable primary liver cancer
PURPOSE This phase II trial is studying how well giving floxuridine and dexamethasone as a hepatic arterial infusion together with bevacizumab works in treating patients with unresectable primary liver cancer
Detailed Description:
OBJECTIVES
Primary
Determine the median time to progression in patients with unresectable primary hepatic malignancy treated with hepatic arterial infusion comprising floxuridine and dexamethasone in combination with systemic bevacizumab
Secondary
Determine the utility of dynamic contrast-enhanced MRI DCE-MRI for assessing changes in tumor perfusion before and during treatment
Correlate DCE-MRI findings with radiographic tumor response
Tertiary
Correlate the expression patterns of vascular endothelial growth factor VEGF receptor VEGFR-1 VEGFR-2 and VEGFR-3 and their cognate ligands including VEGF-A VEGF-B VEGF-C VEGF-D and placenta growth factor PlGF with disease progression and survival after therapy
Assess the pro-angiogenic activity of peripheral blood before and during treatment
Assess tumors for immunohistochemical markers of hypoxia eg hypoxia-inducible factor HIF-1α carbonic anhydrase IX CA IX and glucose transporters Glut-1 and Glut-3 for correlation with initial and treatment-related changes in perfusion and permeability as determined by DCE-MRI
OUTLINE This is an open-label nonrandomized study
Patients undergo placement of the hepatic arterial infusion HAI pump and a cholecystectomy Approximately 2 weeks later patients receive floxuridine and dexamethasone by HAI continuously on days 1-14 and 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 4 weeks in the absence of disease progression or unacceptable toxicity
Patients undergo dynamic contrast-enhanced MRI DCE-MRI on days 1 and 15 of course 1 and then every 8 weeks thereafter
Tumor and nontumor tissue is collected at the time of the HAI pump placement Tissue is examined for the expression of vascular endothelial growth factor VEGF-A -B -C and -D placenta growth factor PlGF and VEGF receptor VEGFR-1 -2 and -3 by immunohistochemistry Peripheral blood is collected at baseline and on day 1 of each course Plasma levels of VEGF-A -B -C and -D are measured by immunoenzyme techniques Blood is also examined by flow cytometry and immunological methods and by protein extraction and analysis of VEGF and VEGFR expression by western blot Immunohistochemical markers of hypoxia in tissue including hypoxia-inducible factor HIF-1α carbonic anhydrase IX CA IX glucose transporters Glut-1 and Glut-3 and Ki-67 are assessed
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 55 patients will be accrued for this study
Primary
Determine the median time to progression in patients with unresectable primary hepatic malignancy treated with hepatic arterial infusion comprising floxuridine and dexamethasone in combination with systemic bevacizumab
Secondary
Determine the utility of dynamic contrast-enhanced MRI DCE-MRI for assessing changes in tumor perfusion before and during treatment
Correlate DCE-MRI findings with radiographic tumor response
Tertiary
Correlate the expression patterns of vascular endothelial growth factor VEGF receptor VEGFR-1 VEGFR-2 and VEGFR-3 and their cognate ligands including VEGF-A VEGF-B VEGF-C VEGF-D and placenta growth factor PlGF with disease progression and survival after therapy
Assess the pro-angiogenic activity of peripheral blood before and during treatment
Assess tumors for immunohistochemical markers of hypoxia eg hypoxia-inducible factor HIF-1α carbonic anhydrase IX CA IX and glucose transporters Glut-1 and Glut-3 for correlation with initial and treatment-related changes in perfusion and permeability as determined by DCE-MRI
OUTLINE This is an open-label nonrandomized study
Patients undergo placement of the hepatic arterial infusion HAI pump and a cholecystectomy Approximately 2 weeks later patients receive floxuridine and dexamethasone by HAI continuously on days 1-14 and 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 4 weeks in the absence of disease progression or unacceptable toxicity
Patients undergo dynamic contrast-enhanced MRI DCE-MRI on days 1 and 15 of course 1 and then every 8 weeks thereafter
Tumor and nontumor tissue is collected at the time of the HAI pump placement Tissue is examined for the expression of vascular endothelial growth factor VEGF-A -B -C and -D placenta growth factor PlGF and VEGF receptor VEGFR-1 -2 and -3 by immunohistochemistry Peripheral blood is collected at baseline and on day 1 of each course Plasma levels of VEGF-A -B -C and -D are measured by immunoenzyme techniques Blood is also examined by flow cytometry and immunological methods and by protein extraction and analysis of VEGF and VEGFR expression by western blot Immunohistochemical markers of hypoxia in tissue including hypoxia-inducible factor HIF-1α carbonic anhydrase IX CA IX glucose transporters Glut-1 and Glut-3 and Ki-67 are assessed
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 55 patients will be accrued for this study
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 |
|---|---|---|---|
| GENENTECH-MSKCC-06114 | None | None | None |
| MSKCC-06114 | None | None | None |