Working… Menu

Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00055692
Recruitment Status : Completed
First Posted : March 7, 2003
Results First Posted : February 29, 2016
Last Update Posted : February 29, 2016
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is to see if bevacizumab works in treating patients who have unresectable nonmetastatic liver cancer that has not spread to the main portal vein. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them.

Condition or disease Intervention/treatment Phase
Adult Primary Hepatocellular Carcinoma Localized Unresectable Adult Primary Liver Cancer Recurrent Adult Primary Liver Cancer Biological: bevacizumab Phase 2

Detailed Description:


I. Determine the efficacy of bevacizumab, in terms of progression-free survival and disease stability and response, in patients with unresectable nonmetastatic hepatocellular cancer (HCC) without main portal vein invasion.

II. Determine the safety of this drug in these patients. III. Assess tumor vascular perfusion kinetics, by dynamic gadolinium-enhanced MRI, in patients before and after treatment with this regimen.

IV. Determine the effect of vascular endothelial growth factor (VEGF)-inhibition by this drug on circulating levels of VEGF and related cytokines that also contribute to HCC pathogenesis (including bFGF, TGF-alpha, and IGF-II) and on potential alterations of these levels on prognostic variables in these patients.

V. Determine the effect of VEGF-inhibition by this drug on hepatic function and hepatitis viral activity in cirrhosis in these patients.

OUTLINE: This is a multicenter, pilot study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment continues every 2 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bevacizumab (RhuMAB-VEGF) In Hepatocellular Cancer For Patients With Unresectable Tumor (Without Invasion Of The Main Portal Vein Or Metastatic Disease) A Phase II Study
Study Start Date : February 2003
Actual Primary Completion Date : January 2008
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: Treatment (bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment continues every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given orally
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Primary Outcome Measures :
  1. Progression-free Survival [ Time Frame: At 6 months ]
  2. Disease Response [ Time Frame: MRI is required at weeks 8, 16 and then every 12 weeks until disease progression ]
    MRI scan is required at weeks 8, 16 and then every 12 weeks until disease progression. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  3. Mean Arterial Enhancement, Per Lesion, as Determined by Dynamic Gadolinium-enhanced Magnetic Resonance Imaging (MRI), Before and Following Bevacizumab Therapy. [ Time Frame: Baseline and 8 weeks after bevacizumab therapy ]
  4. Assessment on Circulating Levels of VEGF Which Also Contribute to HCC Pathogenesis and on Potential Alterations of These Levels in the Setting of VEGF-inhibition [ Time Frame: During treatment ]
  5. To Collect Information on Hepatic Function and Hepatitis Viral Activity in Cirrhosis and Upon Potential Alterations in the Setting of VEGF-inhibition [ Time Frame: During and after treatment ]

Other Outcome Measures:
  1. Disease Stability [ Time Frame: At 6 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed hepatocellular carcinoma

    • Confirmed by needle aspirate, biopsy, or prior surgical resection specimen
  • Clinically confirmed hepatocellular carcinoma defined as follows:

    • Cirrhosis or chronic hepatitis B or C virus infection, with 1 or more hypervascular liver masses more than 2 cm
    • Alpha-fetoprotein (AFP) greater than 400 ng/mL OR greater than 3 times normal and doubling in value during the past 3 months
  • Deemed unresectable

    • Prior surgical resection allowed
    • Recurrence after hepatic resection or other procedure allowed
    • Tumor that extends into branches of the portal or hepatic veins allowed
    • No tumor invading the main portal vein (portal trunk) or inferior vena cava
    • No tumor occupying more than 50% of the liver volume
  • Enlargement/involvement of regional lymph nodes allowed
  • At least 1 unidimensionally measurable lesion at least 20 mm

    • No poorly defined lesions
    • No vague hypervascular patches
  • Child-Pugh class A or compensated Child-Pugh class B liver dysfunction

    • No Child-Pugh class C or uncompensated class B indicated by active encephalopathy, persistent ascites, or prothrombin time greater than 1.5 times normal
    • Prior ascites allowed if manageable with diuretics alone
    • No repeated paracentesis (more than 1 per month)
  • No extrahepatic metastasis
  • No documented brain metastases
  • No history or clinical evidence of CNS disease (e.g., primary brain tumor, seizures uncontrolled with standard medical therapy, or history of stroke)
  • Performance status - ECOG 0-2
  • Absolute neutrophil count greater than 1,500/mm^3
  • Hemoglobin at least 8 g/dL
  • Platelet count at least 75,000/mm^3
  • No prior serious bleeding event (unrelated to liver disease)
  • No bleeding diathesis
  • No coagulopathy
  • Bilirubin no greater than 3 mg/dL
  • Transaminases less than 5 times upper limit of normal (ULN)
  • Albumin at least 2.5 mg/dL
  • PTT less than 4 seconds above ULN
  • INR less than 1.5 (for patients receiving warfarin)
  • Creatinine less than 1.5 g/dL
  • Urine protein less than 500 mg/24hrs*

Exclusion criteria:

  • No thromboembolic event within the past 12 months
  • No clinically significant cardiovascular disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infection requiring parenteral antibiotics
  • No serious non-healing wound/ulcer or bone fracture
  • No variceal bleeding within the past 6 months
  • No malignancy within the past 5 years except localized nonmelanoma skin cancer
  • No ongoing psychiatric or social situation that would preclude study compliance
  • No known hypersensitivity to Chinese hamster ovary cell products
  • No known hypersensitivity to other recombinant human antibodies
  • No more than 1 prior biologic therapy
  • No concurrent interferon
  • No concurrent interleukin-2
  • No more than 1 prior antineoplastic chemotherapy
  • At least 4 weeks since prior invasive surgery, including open biopsy
  • At least 2 weeks since prior needle biopsy (core or fine-needle aspirate)
  • No concurrent hepatic transplant
  • At least 4 weeks since prior anticancer therapy
  • No concurrent platelet-stimulating factors (e.g., oprelvekin)
  • No concurrent full-dose anticoagulants or thrombolytic agents (except as required to maintain patency of pre-existing, permanent indwelling IV catheters)
  • No chronic daily antiplatelet drugs (e.g., aspirin doses of 325 mg/day or higher or non-steroidal anti-inflammatory drugs)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00055692

Layout table for location information
United States, New York
Montefiore Medical Center - Moses Campus
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Abby Siegel Montefiore Medical Center - Moses Campus

Publications of Results:
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00055692     History of Changes
Other Study ID Numbers: NCI-2012-02518
NCI-2012-02518 ( Other Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-5611 ( Other Identifier: NCI/CTEP )
5611 ( Other Identifier: CTEP )
P30CA013330 ( U.S. NIH Grant/Contract )
N01CM62204 ( U.S. NIH Grant/Contract )
N01CM62203 ( U.S. NIH Grant/Contract )
First Posted: March 7, 2003    Key Record Dates
Results First Posted: February 29, 2016
Last Update Posted: February 29, 2016
Last Verified: December 2012
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents, Immunological
Antibodies, Monoclonal
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors