Phase II Study of the A-ICOX Regimen Consisting of Bevacizumab (Avastinâ), Intermittent Dose Capecitabine (Xelodaâ) and Oxaliplatin (Eloxatinâ) in Patients With Untreated Advanced Colorectal Cancer

Inclusion Criteria:

- advanced, surgically unresectable CRC

- measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension(histological confirmation of adenocarcinoma of the colon or
rectum.

ECOG performance status of 0, 1, or 2 Estimated life expectancy of at least 12 weeks.

- chemotherapy prior to the diagnosis of metastatic disease. The chemotherapy regimen
must not have included oxaliplatin or bevacizumab. No prior therapy for metastatic
disease is permitted.

- Evidence of adequate organ function, including:

- Evidence of adequate hepatic function,

- Evidence of adequate renal function INR <1.5 x ULN (unless taking warfarin in which
case it must be in the therapeutic range). Patients on warfarin are allowed to
participate.

- Absence of proteinuria on urine analysis· Patients with a history of prior
non-colorectal malignancies are eligible if they have been disease-free for at least
5 years prior to study entry and are deemed by the physician to be at low risk for
recurrence. Patients with the following cancers are eligible if diagnosed and
treated within the past 5 years: melanoma in situ, and basal cell and squamous cell
carcinoma of the skin.

- Age > 18 yrs.

Exclusion Criteria:

- Any systemic therapy administered for metastatic or locally recurrent disease.
Patients who are considered candidates for surgical resection of metastatic and/or
locally advanced disease.

- Any histology other than adenocarcinoma of the colon or rectum.

- Pregnancy or lactation at the time of patient entry or women of childbearing
potential with no pregnancy test. Eligible patients of reproductive potential (both
sexes) must agree to use adequate contraceptive methods during and for 6 months after
study therapy.

- Serious concomitant medical conditions that, in the opinion of the investigator,
would compromise the safety of the patient or compromise the patient's ability to
complete the study.

- General Medical Concerns History of other disease, metabolic dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug or that
might affect the interpretation of the results of the study or render the subject at
high risk from treatment complications.

- Serious, uncontrolled, concurrent infection.

- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
syndrome.

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study; fine needle aspirations or core biopsies within 7 days prior to
Day 0.

- Proteinuria at baseline or clinically significant impairment of renal function.

- Serious, non healing wound, ulcer, or bone fracture

- Subjects who can not take oral medication