Working…
ClinicalTrials.gov
ClinicalTrials.gov 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.
 
ClinicalTrials.gov Identifier: NCT00055692
Recruitment Status : Completed
First Posted : March 7, 2003
Results First Posted : February 29, 2016
Last Update Posted : February 29, 2016
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 6, 2003
First Posted Date  ICMJE March 7, 2003
Results First Submitted Date  ICMJE August 25, 2015
Results First Posted Date  ICMJE February 29, 2016
Last Update Posted Date February 29, 2016
Study Start Date  ICMJE February 2003
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2016)
  • Progression-free Survival [ Time Frame: At 6 months ]
  • 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
  • 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 ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00055692 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: January 29, 2016)
Disease Stability [ Time Frame: At 6 months ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer
Official Title  ICMJE 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
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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Primary Hepatocellular Carcinoma
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
Intervention  ICMJE Biological: bevacizumab
Given orally
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Study Arms  ICMJE 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.
Intervention: Biological: bevacizumab
Publications * Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knox JJ, Chen H, Clark-Garvey S, Weinberg A, Mandeli J, Christos P, Mazumdar M, Popa E, Brown RS Jr, Rafii S, Schwartz JD. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008 Jun 20;26(18):2992-8. doi: 10.1200/JCO.2007.15.9947.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 20, 2007)
46
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2009
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT00055692
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Abby Siegel Montefiore Medical Center - Moses Campus
PRS Account National Cancer Institute (NCI)
Verification Date December 2012

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