VEGF Trap in Treating Patients With Previously Treated Metastatic Colorectal Cancer

This is an interventional treatment trial for Recurrent Colon Cancer Read More

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