RATIONALE: VEGF Trap may stop the growth of solid tumors or non-Hodgkin's lymphoma by
stopping blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of intravenous VEGF
Trap in treating patients with relapsed or refractory advanced solid tumors or non-Hodgkin's
- Determine the safety and tolerability of intravenous VEGF Trap in patients with
relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.
- Determine the maximum tolerated intravenous dose of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the ability of this drug to bind circulating vascular endothelial growth
factor in these patients.
- Determine, preliminarily, the ability of this drug to alter tumor blood flow and tumor
vascular permeability in these patients.
- Determine whether antibodies to this drug develop in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive VEGF Trap IV over 1 hour on days 1 and 15 for a total of 2 doses.
Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6
patients are treated at that dose level.
In the absence of dose-limiting toxicity, patients with stable disease or partial or
complete remission may continue to receive VEGF Trap on a separate extension protocol.
Patients are followed at weeks 1, 3, and 7 and then at 3 months.
PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.
- Histologically confirmed diagnosis of one of the following:
- Non-Hodgkin's lymphoma
- Primary or metastatic solid tumor located, by radiography, in at least one of
the following sites:
- Soft tissue
- Other site that is suitable for delayed contrast-enhanced MRI (e.g.,
peripheral lung field)
- Relapsed or refractory (including unresectable) disease
- Patients with solid tumors must have failed all curative chemotherapeutic
- Patients with non-Hodgkin's lymphoma must be refractory to at least 2 standard
chemotherapeutic regimens and rituximab
- Not amenable to available conventional therapies AND no standard therapy exists
- Measurable disease
- No prior or concurrent CNS metastases (brain or leptomeningeal)
- No primary intracranial tumor by MRI or CT scan
- No histologically confirmed squamous cell carcinoma of the lung
- 18 and over
- ECOG 0-2
- Not specified
- WBC ≥ 3,500/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 100,000/mm^3
- No severe or uncontrolled hematologic condition
- Bilirubin ≤1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- PT and PTT normal
- INR normal
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
- Creatinine ≤ ULN
- Urine protein/creatinine ratio ≤ 1
- No severe or uncontrolled renal condition
- No clinically significant acute electrocardiographic abnormalities
- LVEF normal by echocardiogram or MUGA within the past 12 months if there was prior
exposure to anthracyclines
- No untreated or uncontrolled hypertension
- No blood pressure > 150/100 mm Hg (despite treatment)
- No isolated systolic hypertension (i.e., systolic blood pressure > 180 mm Hg on at
least 2 determinations [on separate days] within the past 3 months)
- No New York Heart Association class II - IV heart disease
- No active coronary artery disease requiring acute medical management
- No angina requiring acute medical management
- No congestive heart failure requiring acute medical management
- No ventricular arrhythmia requiring acute medical management
- No stroke or transient ischemic event within the past 6 months
- No prior or concurrent peripheral vascular disease
- No angiographically or ultrasonographically documented arterial or venous
- No symptomatic claudication
- No symptomatic orthostatic hypotension
- No other severe or uncontrolled cardiovascular condition
- No severe or uncontrolled pulmonary condition
- No pulmonary embolism within the past 6 months
- HIV negative
- No severe or uncontrolled immunologic condition
- No active current infection requiring antibiotics
- No prior hypersensitivity reaction to any recombinant proteins, including VEGF Trap
- No severe or uncontrolled gastrointestinal or musculoskeletal condition
- No psychiatric condition or adverse social circumstance that would preclude study
- No other condition that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception during and for 3
months after study treatment
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior participation in a VEGF Trap, interleukin-1 Trap, or interleukin-4/13 Trap
- At least 3 weeks since prior immunotherapy and recovered
- No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy and recovered
- No concurrent adrenal corticosteroids except low-dose replacement therapy
- No concurrent systemic hormonal contraceptive agents
- At least 3 weeks since prior radiotherapy and recovered
- At least 3 weeks since prior major or laparoscopic surgery and recovered
- More than 6 months since prior surgical procedure for correction or prophylaxis of
peripheral vascular insufficiency or cerebral ischemic events
- More than 30 days since prior investigational drugs
- No concurrent anticoagulant or antiplatelet drugs (e.g., warfarin, heparin, or
aspirin) other than low-dose (1 mg) warfarin for maintaining patency of venous access
- No concurrent non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2
- No other concurrent anticancer investigational agents
- No other concurrent anticancer therapy