Bevacizumab in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary 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. Secondary 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.

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

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: Bevacizumab (Avastin)


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: 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 PRIOR CONCURRENT THERAPY: 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab (Avastin)<br>Bevacizumab given and then BP checked and skin biopsies obtained. | Biological: Bevacizumab (Avastin)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific