Bevacizumab in Treating Patients With Advanced Solid Tumors

Herbert Hurwitz, MD

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Biological: Bevacizumab (Avastin)

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00416637

DUMC-4907-05-6R2

GENENTECH-DUMC-4907-05-6R2

CDR0000449969 (Other Identifier)

Pro00008011

Details and patient eligibility

About

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.

Full description

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.

Enrollment

27 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)