Chemoembolization and Bevacizumab in Treating Patients With Liver Cancer That Cannot Be Removed With Surgery
RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, cisplatin, and mitomycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Monoclonal antibodies, such as bevacizumab, can kill any tumor cells that are left after chemoembolization by blocking their ability to grow and spread.
PURPOSE: This randomized phase II trial is studying to see if chemoembolization followed by bevacizumab works better than chemoembolization alone in treating patients who have liver cancer that cannot be removed with surgery.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Of rhuMAb VEGF (BEVACIZUMAB) In Patients With Hepatocellular Carcinoma Receiving Chemoembolization|
- Neovessel Formation as Measured by Angiogram at 14 Weeks [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]Angiograms were assessed for changes in vascularity. The numbers indicate how many subjects in each group showed neovessel formation.
- Progression Free Survival [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Progression free survival (PFS) at 16 weeks (end of the core phase).
- Assess the Toxicities of Bevacizumab in Patients With Liver Function Impairment [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
- Assess Pharmakokinetics of Bevacizumab in Liver Disease [ Time Frame: day 85 ] [ Designated as safety issue: No ]bevacizumab serum concentrations
- Measure (Vascular Endothelial Growth Factor)VEGF Before and After TACE With and Without Bevacizumab [ Time Frame: 21 days after TACE ] [ Designated as safety issue: No ]
|Study Start Date:||June 2003|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I-bevacizumab
Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning 1 week prior to the first chemoembolization at a dose of 10 mg/kg. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Given IV, 10mg/kg evey two weeks starting 1 week prior to the first chemoembolization.
Patients crossed over to the Bevacizumab arm will receive Bevacizumab after week 14 at the same dose.
Other Name: Avastin
No Intervention: Arm II-chemoembolization
chemoembolization as part of standard of care
- Compare neovessel formation at 8 and 14 weeks after hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma treated with bevacizumab versus no bevacizumab (observation after chemoembolization only).
- Compare time to progression, objective response rate, and tumor marker progression in patients treated with these regimens.
- Determine the pharmacokinetics of bevacizumab in patients with liver function impairment.
- Determine the toxic effects of this drug in these patients.
- Compare the cancer biomarker pattern of peripheral blood cells and plasma before and after chemoembolization in patients treated with these regimens.
OUTLINE: This is a randomized, open-label study.
All patients receive hepatic artery chemotherapy (chemoembolization) comprising doxorubicin HCl liposome, cisplatin, and mitomycin on day 8 and possibly on day 92. Patients are then randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning 1 week prior to the first chemoembolization. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients do not receive bevacizumab. Patients in arm II may cross-over receive bevacizumab as in arm I if recurrent tumor is evident at week 14 by CT scan or MRI or a 50% or greater increase in AFP level has occurred since day 8 chemoembolization.
PROJECTED ACCRUAL: A total of 30 patients (15 per treatment arm) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00049322
|United States, California|
|Jonsson Comprehensive Cancer Center at UCLA|
|Los Angeles, California, United States, 90095-1781|
|Principal Investigator:||Carolyn Britten, MD||Jonsson Comprehensive Cancer Center|