Bevacizumab in Treating Patients With Advanced Solid Tumors

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. Identifier: NCT00416637
Recruitment Status : Completed
First Posted : December 28, 2006
Last Update Posted : July 7, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Herbert Hurwitz, MD, Duke University

Brief Summary:

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor .

PURPOSE: This phase I trial is studying how well bevacizumab works in treating patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Biological: Bevacizumab (Avastin) Phase 1

Detailed Description:



  • Determine whether anti-vascular epidermal growth factor (VEGF) treatment comprising bevacizumab causes changes in endothelial cell function, as measured by brachial reactivity, and changes in nitric oxide (NOx), as measured by plasma/urinary/exhaled NOx levels, in patients with advanced solid tumors.
  • Determine whether anti-VEGF-related changes in blood pressure correlate with changes in brachial reactivity and NOx levels.


  • Evaluate anti-angiogenic effects of bevacizumab in neovascular tissue in the wound angiogenesis model.
  • Correlate inhibition of wound angiogenesis with changes in VEGF-receptor 2 phosphorylation status and changes in NOx synthase expression.
  • Describe the mean and associated variability of other plasma and urine markers known to be associated with vascular reactivity, endothelial function, and/or tumor angiogenesis.
  • Describe, preliminarily, whether these changes correlate with changes in blood pressure, brachial reactivity, NOx levels, or wound angiogenesis.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29. After the third dose of bevacizumab, patients may receive additional bevacizumab in combination with chemotherapy in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biomarker and Clinical Evaluation of Bevacizumab (Avastin) to Determine the Role of Nitric Oxide in Anti-VEGF Therapy
Study Start Date : January 2004
Actual Primary Completion Date : March 2006
Actual Study Completion Date : March 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Bevacizumab (Avastin)
Bevacizumab given and then BP checked and skin biopsies obtained.
Biological: Bevacizumab (Avastin)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed solid tumor

    • Metastatic or unresectable disease
  • Standard curative or palliative measures do not exist or are no longer effective OR treatment with standard chemotherapy plus bevacizumab is appropriate* NOTE: *It must be judged clinically appropriate by the treating physician to delay combination treatment for the 6 weeks needed for study participation
  • Patients with squamous cell non-small cell lung cancer are ineligible


  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 2,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if known liver metastases are present)
  • Creatinine clearance ≥ 50 mL/min
  • No proteinuria at baseline

    • Patients with ≥ 1+ proteinuria during screening should undergo a timed 12- or 24-hour urine collection, which must be an adequate collection and must demonstrate < 500 mg protein/24 hr to be eligible for the study
  • Not pregnant or nursing

    • No nursing for ≥ 4 months after completion of study treatment
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 4 months after completion of study treatment
  • No arterial thromboembolic events within the past 6 months, including any of the following:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina
    • Myocardial infarction
    • Clinically significant peripheral vascular disease
  • No venous thromboembolic event within the past 3 months
  • No clinically significant cardiovascular disease
  • No uncontrolled hypertension
  • No New York Heart Association class II or greater congestive heart failure
  • No serious cardiac arrhythmia requiring medication

    • Atrial or supraventricular tachycardias that are well controlled with beta blockers or calcium channel blockers are allowed
    • Chronic pacemakers allowed
  • No presence of bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 4 weeks
  • No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications


  • No administration of nitrates within the past week
  • At least 2 weeks since prior and no concurrent antihypertensive agent(s)

    • Must have stable blood pressure (BP) (BP < 160/100 mm Hg) within the past 2 weeks
    • Must be asymptomatic within the past 2 weeks
  • No open biopsy within the past 14 days
  • No fine needle aspirations other than in the breast within the past 7 days
  • No placement of a vascular access device within the past 7 days
  • No major surgical procedure within the past 4 weeks
  • No chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No radiotherapy within the past 4 weeks
  • No previous treatment with bevacizumab
  • No need for major surgical procedure during the course of the study
  • No other cancer immunotherapy or biologic therapy while on the study
  • No concurrent or recent (within past 10 days) use of full-dose oral or parenteral anticoagulants (heparin > 10,000/day or an INR > 1.5) or thrombolytic agents

    • 1 mg of warfarin is permitted as required to maintain patency of preexisting, permanent indwelling IV catheters
  • No chronic, daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications (of the kind known to inhibit platelet function at doses used to treat chronic inflammatory diseases)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00416637

Sponsors and Collaborators
Herbert Hurwitz, MD
National Cancer Institute (NCI)
Principal Investigator: Herbert I. Hurwitz, MD Duke Cancer Institute

Responsible Party: Herbert Hurwitz, MD, Associate Professor of Medicine, Duke University Identifier: NCT00416637     History of Changes
Other Study ID Numbers: Pro00008011
CDR0000449969 ( Other Identifier: NCI )
First Posted: December 28, 2006    Key Record Dates
Last Update Posted: July 7, 2016
Last Verified: July 2016

Keywords provided by Herbert Hurwitz, MD, Duke University:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents