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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

Phase 2
18 Years
Not Enrolling
Adult Primary Hepatocellular Carcinoma, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

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Trial Information

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


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.

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

- 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)

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

At 6 months

Safety Issue:


Principal Investigator

Abby Siegel

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

February 2003

Completion Date:

Related Keywords:

  • Adult Primary Hepatocellular Carcinoma
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular



Montefiore Medical Center Bronx, New York  10467-2490