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Biomarker and Clinical Evaluation of Bevacizumab (Avastin) to Determine the Role of Nitric Oxide in Anti-VEGF Therapy

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Biomarker and Clinical Evaluation of Bevacizumab (Avastin) to Determine the Role of Nitric Oxide in Anti-VEGF Therapy



- 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

- 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.

Inclusion Criteria


- 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

- 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

- 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

- 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)

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Herbert I. Hurwitz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms