RATIONALE: VEGF Trap may stop the growth of solid tumors or non-Hodgkin's lymphoma by stopping blood flow to the tumor.

PURPOSE: Phase I trial to study the effectiveness of intravenous VEGF Trap in treating patients who have relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
Cancer	Drug: VEGF Trap  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy  Procedure: targeted fusion protein therapy	Phase I

OBJECTIVES: Primary

• Determine the safety and tolerability of intravenous VEGF Trap in patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.

Secondary

• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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:
• Liver
• Soft tissue
• Pelvis
• 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 regimens
• 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

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• 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

Hepatic

• 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

Renal

• Creatinine ≤ ULN
• Urine protein/creatinine ratio ≤ 1
• No severe or uncontrolled renal condition

Cardiovascular

• 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 occlusive event
• No symptomatic claudication
• No symptomatic orthostatic hypotension
• No other severe or uncontrolled cardiovascular condition

Pulmonary

• No severe or uncontrolled pulmonary condition
• No pulmonary embolism within the past 6 months

Immunologic

• 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

Other

• No severe or uncontrolled gastrointestinal or musculoskeletal condition
• No psychiatric condition or adverse social circumstance that would preclude study participation
• 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: Biologic therapy

• See Disease Characteristics
• No prior participation in a VEGF Trap, interleukin-1 Trap, or interleukin-4/13 Trap clinical trial
• At least 3 weeks since prior immunotherapy and recovered
• No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy and recovered

Endocrine therapy

• No concurrent adrenal corticosteroids except low-dose replacement therapy
• No concurrent systemic hormonal contraceptive agents

Radiotherapy

• At least 3 weeks since prior radiotherapy and recovered

Surgery

• 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

Other

• 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 devices
• No concurrent non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 (COX-2) inhibitors
• No other concurrent anticancer investigational agents
• No other concurrent anticancer therapy

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Jakob Dupont, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000360856; MSKCC-03137; REGENERON-VGFT-ST-0202
Record last reviewed:  August 2004
Record first received:  May 14, 2004
ClinicalTrials.gov Identifier:  NCT00083213
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-17