- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00055692
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
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New York
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Bronx, New York, United States, 10467-2490
- Montefiore Medical Center - Moses Campus
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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Given orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: At 6 months
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At 6 months
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Disease Response
Time Frame: MRI is required at weeks 8, 16 and then every 12 weeks until disease progression
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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
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MRI is required at weeks 8, 16 and then every 12 weeks until disease progression
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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
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Baseline and 8 weeks after bevacizumab therapy
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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
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During treatment
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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
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During and after treatment
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Disease Stability
Time Frame: At 6 months
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At 6 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Abby Siegel, Montefiore Medical Center - Moses Campus
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Carcinoma, Hepatocellular
- Liver Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibodies
- Immunoglobulins
- Bevacizumab
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
Other Study ID Numbers
- NCI-2012-02518 (Other Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA013330 (U.S. NIH Grant/Contract)
- N01CM62204 (U.S. NIH Grant/Contract)
- N01CM62203 (U.S. NIH Grant/Contract)
- NCI-5611 (Other Identifier: NCI/CTEP)
- 5611 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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