Safety and Efficacy Study Using Bevacizumab, Capecitabine and Oxaliplatin for Colorectal Cancer

Inclusion Criteria:

• advanced, surgically unresectable CRC

• measurable disease, defined as at least one lesion that can be accurately measured inat least one dimension(histological confirmation of adenocarcinoma of the colon orrectum. 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 regimenmust not have included oxaliplatin or bevacizumab. No prior therapy for metastaticdisease 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 whichcase it must be in the therapeutic range). Patients on warfarin are allowed toparticipate.

• Absence of proteinuria on urine analysis· Patients with a history of priornon-colorectal malignancies are eligible if they have been disease-free for at least 5years prior to study entry and are deemed by the physician to be at low risk forrecurrence. Patients with the following cancers are eligible if diagnosed and treatedwithin the past 5 years: melanoma in situ, and basal cell and squamous cell carcinomaof 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/orlocally 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 potentialwith no pregnancy test. Eligible patients of reproductive potential (both sexes) mustagree to use adequate contraceptive methods during and for 6 months after studytherapy.

• Serious concomitant medical conditions that, in the opinion of the investigator, wouldcompromise the safety of the patient or compromise the patient's ability to completethe study.

• General Medical Concerns History of other disease, metabolic dysfunction, physicalexamination finding, or clinical laboratory finding giving reasonable suspicion of adisease or condition that contraindicates the use of an investigational drug or thatmight affect the interpretation of the results of the study or render the subject athigh risk from treatment complications.

• Serious, uncontrolled, concurrent infection.

• Lack of physical integrity of the upper gastrointestinal tract or malabsorptionsyndrome.

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 daysprior to Day 0, or anticipation of need for major surgical procedure during the courseof 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