Inclusion Criteria:

i) Histological diagnosis of colorectal cancer ii) Metastatic disease that is not
resectable iii) Age > 18 years iv) Any patient in whom the investigator considers
immediate cytotoxic chemotherapy is not required.

v) Measurable and/or non-measurable disease as assessed by CT scan vi) ECOG performance
status 0, 1 or 2. vii) No prior chemotherapy except for adjuvant chemotherapy. viii)
Adequate bone marrow function with platelets > 100 X 109/l; neutrophils > 1.5 X 109/l ix)
Adequate renal function, with calculated creatinine clearance >40 ml/min (Cockcroft and
Gault).

x) Adequate hepatic function with serum total bilirubin < 1.5 X upper limit of normal
range xi) Life expectancy of at least 12 weeks xii) No other concurrent uncontrolled
medical conditions xiii) No other malignant disease apart from non-melanotic skin cancer
or carcinoma in situ of the uterine cervix or any other cancer treated with curative
intent >2 years previously without evidence of relapse xiv) Women and partners of women of
childbearing potential must agree to use adequate contraception xv) Written informed
consent including consent for biomarker studies

Exclusion Criteria:

i) Medical or psychiatric conditions that compromise the patient's ability to give
informed consent or to complete the protocol ii) Uncontrolled hypertension iii) Prior
treatment with VEGF inhibitors or angiopoietin inhibitors iv) Active bleeding disorders
within the last 6 months v) Participation in any investigational drug study within the
previous 4 weeks vi) Patients with uncontrolled clinically significant cardiac disease,
arrhythmias or angina pectoris vii) Patients with a history of arterial or venous
thrombosis within the last 12 months viii) Concurrent or prior (within 1 week before
enrollment) anticoagulation therapy. The concurrent use of low molecular weight heparin
or low dose warfarin (ie, 1 mg daily) for prophylaxis against thrombosis is acceptable
while on study ix) Regular use of aspirin (>325mg/day) or NSAIDs (low dose aspirin (<325
mg/d), or occasional use of NSAIDs is acceptable) x) Treatment with immune modulators such
as cyclosporine or tacrolimus within the previous 4 weeks xi) CNS metastases xii) Major
surgical procedure within the last 28 days xiii) Minor surgical procedure, placement of
access device, or fine needle aspiration within the last 7 days xiv) Serious non-healing
wound, ulcer or bone fracture xv) 24 hour urinary protein > 1g/ 24 hours ( performed if
urine dipstick > 1+ ) xvi) Pregnancy or lactation