Adult Primary Hepatocellular CarcinomaPhase 2NCT00055692
Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer
A Phase 2 study testing bevacizumab in people with Adult Primary Hepatocellular Carcinoma and Localized Unresectable Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Primary Hepatocellular Carcinoma, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- What is being tested?
- bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Dec 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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*
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467-2490
About this study
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
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.
Read the detailed description
OBJECTIVES:
- 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.
- 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.
- Conditions
- Adult Primary Hepatocellular Carcinoma, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- Being tested
- bevacizumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bevacizumab) | Experimental | 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. Receives: Biological: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Measured: At 6 months
Disease Response
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
Measured: MRI is required at weeks 8, 16 and then every 12 weeks until disease progression
Mean Arterial Enhancement, Per Lesion, as Determined by Dynamic Gadolinium-enhanced Magnetic Resonance Imaging (MRI), Before and Following Bevacizumab Therapy.
Measured: 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
Measured: During treatment
To Collect Information on Hepatic Function and Hepatitis Viral Activity in Cirrhosis and Upon Potential Alterations in the Setting of VEGF-inhibition
Measured: During and after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2003 (estimated)
- Study startFeb 2003
- Primary completionJan 2008
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Primary Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Abby Siegel, Principal investigator, Montefiore Medical Center - Moses Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00055692
- Sponsor's protocol ID
- NCI-2012-02518
- Other IDs
- NCI-2012-02518, NCI-5611, 5611, P30CA013330, N01CM62204, N01CM62203
- Status last verified
- Dec 2012
- First submitted
- 6 Mar 2003
- Last updated
- 29 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 18565886
Study at a glance
From the registry record, last updated by the sponsor on 29 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00055692
- Acronym / sponsor ID
- NCI-2012-02518
- Conditions
- Adult Primary Hepatocellular Carcinoma, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2003
- Primary completion
- Jan 2008 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 7 Mar 2003 (estimated)
- Results
- Posted 29 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bevacizumab) | Experimental | Biological: bevacizumabPatients receive bevacizumab IV over 30-90 minutes on day 1. Treatment continues every 2 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Histologically confirmed hepatocellular carcinoma
- Clinically confirmed hepatocellular carcinoma defined as follows:
- Deemed unresectable
- Enlargement/involvement of regional lymph nodes allowed
- At least 1 unidimensionally measurable lesion at least 20 mm
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumabAlso: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGFGiven orally | Biological | Treatment (bevacizumab) |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18565886Siegel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abby Siegel principal investigator
Montefiore Medical Center - Moses Campus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab in people with Adult Primary Hepatocellular Carcinoma and Localized Unresectable Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: At 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00055692, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Feb 2016.