Bevacizumab in Treating Patients With Advanced Solid Tumors
This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Herbert Hurwitz, MD, Duke University Medical Center
First received: December 27, 2006
Last updated: February 9, 2016
Last verified: February 2016
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.
Unspecified Adult Solid Tumor, Protocol Specific
||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Biomarker and Clinical Evaluation of Bevacizumab (Avastin) to Determine the Role of Nitric Oxide in Anti-VEGF Therapy
| Estimated Enrollment:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||March 2006 (Final data collection date for primary outcome measure)
Avastin given and then BP was checked and skin biopsies were obtained.
- 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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00416637
Herbert Hurwitz, MD
National Cancer Institute (NCI)
||Herbert I. Hurwitz, MD
||Duke Cancer Institute
||Herbert Hurwitz, MD, Associate Professor of Medicine, Duke University Medical Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 27, 2006
||February 9, 2016
||United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by Duke University:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 26, 2016
Angiogenesis Modulating Agents
Physiological Effects of Drugs