VEGF Trap in Treating Patients With Previously Treated Metastatic Colorectal Cancer
Condition: Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: aflibercept
Intervention description: Given intravenously
Intervention MeSH terms: Aflibercept; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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