Clinical trial NCT00407654 (phase 2, status: completed)
Conditions: recurrent colon cancer, recurrent rectal cancer, stage iv colon cancer, stage iv rectal cancer
ICD codes: C18.2, C18.4, C18.6, C18.7, C18.9, D12.2, D12.3, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2
Drugs: aflibercept
SMILES: N[C@@H](CCCNC(N)=N)C(O)=O
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