This phase II trial is studying how well VEGF Trap works in treating patients with previously treated metastatic colorectal cancer. VEGF Trap may stop the growth of colorectal cancer by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. Determine the response rate (complete and partial) in patients with previously treated metastatic colorectal cancer treated with VEGF Trap.

II. Determine the incidence of disease stabilization, in terms of 4-month progression-free survival, in patients treated with this drug.

SECONDARY OBJECTIVES:

I. Determine the median survival time of patients treated with this drug. II. Determine the 1-year survival rate and stable disease rate in patients treated with this drug.

III. Determine the response or stable disease duration in patients treated with this drug.

IV. Determine the toxicity of this drug in these patients. V. Determine the time to disease progression in patients treated with this drug.

VI. Determine if changes in free VEGF Trap levels correlate with response or toxicity.

OUTLINE: This is a multicenter, open-label study.

Patients are stratified according to prior bevacizumab treatment (yes vs no). Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection at the beginning of each course and at 60 days after completion of study treatment. Samples are analyzed by immunoenzyme techniques to determine the pharmacokinetics of VEGF Trap.

After completion of study treatment, patients are followed at 30 and 60 days and then every 3 months thereafter.

Inclusion Criteria:

• histologically/cytologically confirmed metastatic colorectal metastatic cancer
• measurable disease (at least 1 lesion accurately measured in at least 1 dimension (longest diameter) as>20mm with conventional techniques or as >10mm with spiral CT scan
• >=4 weeks from major surgery
• at least 1prior line of systemic therapy for metastatic disease. Prior treatment with anti-epidermal growth factor receptor inhibitors is allowed. Last dose >=4 weeks prior to randomization
• Two cohorts: 1) bevacizumab naïveand; 2) bevacizumab treated
• May have received prior thymidylate synthetase inhibitor concurrently with radiation as "radiation sensitizer". Last dose >=4 weeks prior to randomization
• Prior radiation treatment >=4 weeks prior to randomization
• Age>=18 years
• Life expectancy >=3 months
• ECOG<=2 (Karnofsky=60%)
• leukocytes >3.0x10^9/L
• absolute neutrophil count >1.5 x 10^9/L
• platelets>75x10^9/L
• INR <1.5 unless on warfarin
• total bilirubin within 1.5xULN
• AST/ALT≤2.5 X institution ULN
• creatinine≤1.5xULN OR creatinine clearance >60mL/min/1.73m2 for patients with creatinine levels above1.5x institution limits
• Urinalysis negative for protein OR 24h urine for protein <500 mg
• full-dose anticoagulants with PT INR >1.5 eligible provided that: a) patient is therapeutic on stable dose of warfarin or low molecular weight heparin; b) patients on warfarin, the upper target for INR is <=3; c) no active bleeding/pathological condition carrying high bleeding risk
• Eligibility of patients receiving medications known to affect activity/PK of VEGF Trap will be determined by PI
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of VEGF Trap therapy
• Ability to understand/willingness to sign written informed consent

Exclusion Criteria:

• chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas/mitomycin C) prior to study entry
• Other investigational agents concurrently
• History of prior anti-angiogenic therapy other than bevacizumab
• Evidence of CNS disease
• Known hypersensitivity to Chinese hamster ovary cell products/other recombinant human antibodies, and patients with a history of allergic reactions attributed to compounds of similar chemical/biologic composition to other agents used in the study.
• Serious/non-healing wound/ulcer/bone fracture
• History of abdominal fistula/GI perforation/bowel obstruction/intraabdominal abscess within 28 days of treatment
• major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
• anticipation of need for major surgical procedures during study
• core biopsy within 7 days prior to Day 1 therapy
• Patients with clinically significant cardiovascular disease
• Evidence of bleeding diathesis or coagulopathy
• PT INR >1.5 unless the patient is on full-dose warfarin
• Use of thrombolytic agents within 1 month of study initiation
• Significant Proteinuria (>500mg/24h): Urine protein should be screened by random urinalysis for protein. If dipstick positive (>1+), 24-hour urine protein should be obtained and if >500mg/24 h, patient will be excluded.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study
• Pregnant women
• HIV-positive patients on combination antiretroviral therapy are ineligible because of potential for PK interactions with VEGF Trap