A Phase II Study Of rhuMAb VEGF (BEVACIZUMAB) In Patients With Hepatocellular Carcinoma Receiving Chemoembolization
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Liver Cancer
- Sponsor
- Jonsson Comprehensive Cancer Center
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Neovessel Formation as Measured by Angiogram at 14 Weeks
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
OBJECTIVES: * 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \> 18 year old
- •Histologically or cytologically documented HCC
- •Patients must have bi-dimensional measurable disease by CT or MRI scan that does not exceed 50% of the liver parenchyma
- •Patients must be considered clinical candidates for chemoembolization, with at least one lesion \> 3cm and no lesion \> 15cm in its longest diameter
- •Patients awaiting cadaveric orthotopic liver transplantation are eligible if they meet all other criteria. These patients must have a model for end-stage liver disease priority score \< 28 points at entry
- •Cirrhosis Child-Pugh class A or B
- •Patients with documented grad III varices or prior history of UGI bleeding will require endoscopic evaluation prior to treatment under this protocol.
- •Platelet count equal or greater than 60,000/μL
- •Female patients must use effective contraception, be surgically sterile or be postmenopausal; male patients must be using barrier contraception or be surgically sterile
- •Patients must be willing and able to comply with all study requirements and have signed the informed consent
Exclusion Criteria
- •Previous history of liver transplantation
- •Fibrolamellar histology
- •Prior antiangiogenesis therapy
- •Presence of extrahepatic disease
- •Presence of biliary obstruction defined as biliary dilatation and total bilirubin \> 2.5mg/dl
- •Thrombosis of the main portal vein
- •Absolute contraindications to doxorubicin, mitomycin-C, cisplatin, iodinated contrast material, Avitene or dexamethasone treatment
- •Other active malignancies during the past year (except for non-melanoma skin cancer or in situ carcinomas)
- •ECOG PS\> 2 or life expectancy \< 12 weeks
- •History or evidence upon physical examination of CNS disease
Outcomes
Primary Outcomes
Neovessel Formation as Measured by Angiogram at 14 Weeks
Time Frame: 14 weeks
Angiograms were assessed for changes in vascularity. The numbers indicate how many subjects in each group showed neovessel formation.
Secondary Outcomes
- Assess the Toxicities of Bevacizumab in Patients With Liver Function Impairment(16 weeks)
- Progression Free Survival(16 weeks)
- Measure (Vascular Endothelial Growth Factor)VEGF Before and After TACE With and Without Bevacizumab(21 days after TACE)
- Assess Pharmakokinetics of Bevacizumab in Liver Disease(day 85)