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Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00055692
First received: March 6, 2003
Last updated: October 10, 2014
Last verified: December 2012

March 6, 2003
October 10, 2014
February 2003
December 2009   (final data collection date for primary outcome measure)
  • Progression-free survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
  • Disease stability [ Time Frame: From the start of treatment until disease progression, assessed up to 6 years ] [ Designated as safety issue: No ]
  • Disease response [ Time Frame: From the time measurement criteria for response (CR or PR) are achieved until the first documentation of progression or recurrence, assessed up to 6 years ] [ Designated as safety issue: No ]
  • Change in tumor vascular perfusion kinetics, as determined by dynamic gadolinium-enhanced magnetic resonance imaging (MRI) [ Time Frame: From baseline to up to 6 years ] [ Designated as safety issue: No ]
  • Change in VEGF and related cytokines [ Time Frame: From baseline to up to 6 years ] [ Designated as safety issue: No ]
  • Effect of VEGF-inhibition on liver function and hepatitis viral activity in cirrhosis [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00055692 on ClinicalTrials.gov Archive Site
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Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer
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

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.

OBJECTIVES:

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Primary Hepatocellular Carcinoma
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Biological: bevacizumab
    Given orally
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Other: laboratory biomarker analysis
    Correlative studies
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.
Interventions:
  • Biological: bevacizumab
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
December 2009
December 2009   (final data collection date for primary outcome measure)

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 (porta-hepatis) 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*
  • No thromboembolic event within the past 12 months including the following:

    • Stroke
    • Myocardial infarction
    • Transient ischemic attack
    • Angina
  • No clinically significant cardiovascular disease including the following:

    • Uncontrolled hypertension
    • Unstable angina
    • Congestive heart failure (New York Heart Association grade II-IV)
    • Serious cardiac arrhythmia requiring medication
    • Grade II or greater peripheral vascular disease within the past year
  • No deep vein thrombosis within the past year
  • No pulmonary embolus within the past year
  • 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

    • Prior esophageal varices allowed provided the following criteria are met:

      • Specific therapy (i.e., banding or sclerotherapy) has been received
      • No bleeding within the past 6 months
      • Varices remaining obliterated, minimal, or grade 1 (involving less than 33% of luminal diameter)* by re-endoscopy within the past 4 weeks
  • 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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00055692
NCI-2012-02518, NCI-2012-02518, NCI-5611, CDR0000270798, MTS-1002-532, 5611, P30CA013330, N01CM62204, N01CM62203
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Abby Siegel Montefiore Medical Center - Moses Campus
National Cancer Institute (NCI)
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP